bims-scepro 2026-08-30 papers

bims-scepro

Biomed News

on Stem cell proteostasis

Issue of 2026–08–30
nineteen papers selected by
William Grey, University of York

Hematopoietic Stem Cell Metabolism during Stress and Aging.
Ferroptotic stress promotes hematopoietic stem cell aging through S1P-dependent epigenetic and lipid remodeling.
Inhibition of nucleoporin 214 depletes leukemia stem cells by promoting heme catabolism and lipid peroxidation.
Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells.
Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia.
Cheminformatic identification of small molecules targeting acute myeloid leukemia.
IL-1-mediated cancer-adapted hematopoiesis in aging and clonal hematopoiesis.
Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1.
Differential Correlation Across Subpopulations of Single Cells in Subtypes of Acute Myeloid Leukemia.
PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.
Evolution in the cryopreservation of hematopoietic stem cells.
Single-cell chromatin profiling reveals relapse-related priming in pediatric acute myeloid leukemia.
Maternal and Neonatal Factors Impacting the Volume and Cellular Composition of Umbilical Cord Blood.
Interpreting cord blood transplant outcomes in BMT CTN 1702.
From Single Cells to Diagnosis: Proteomics Technologies in the Multi-Omics Landscape of Rare and Mitochondrial Diseases.
Dynamic Landscape Analysis of cell fate decisions provides predictive models of neural development from single-cell data.
Spatial profiling of the spleen in mouse and human myelofibrosis reveals complement-driven immune-stromal interactions as a therapeutic target.
Splenic extramedullary hematopoiesis in myelofibrosis is shaped by transcriptomic and epigenetic dysregulation.
usiGrabber: automating the curation of proteomics spectra data at scale, making large datasets ready for use in machine learning systems.

Adv Geriatr Med Res. 2026 Sep;pii: e260018. [Epub ahead of print]8(3):

Hematopoietic Stem Cell Metabolism during Stress and Aging.

Devyani Sharma, Marie-Dominique Filippi.

  Hematopoietic stem cells (HSCs) support the lifelong production of blood but undergo substantial changes during aging. Aging causes a progressive decline in the repopulation ability of HSC with changes in the proportion of myeloid and lymphoid lineages. Metabolic remodeling is increasingly recognized not only as a consequence of HSC aging but also as an active contributor to age-associated changes in HSC function. Quiescent HSCs have low metabolic activity, in contrast with their highly proliferative progeny. During regeneration, drastic metabolic remodeling enables HSC to exit quiescent and proliferate to sustain blood production for emergency hematopoiesis. Metabolic activity drifts during aging. Changes in glycolysis, mitochondrial activity, and lysosomal functions all contribute to a slow decline of the hematopoietic system. In this review, we focus on the metabolic needs of HSCs, how they control their quiescence and proliferation, and how a metabolic drift contributes to HSC aging.

Keywords:  HSC aging; bone marrow niche; fatty acid oxidation; hematopoietic stem cells; metabolic remodeling; mitochondrial metabolism; mitochondrial quality control; oxidative phosphorylation; stem cell quiescence; stress hematopoiesis

DOI:  https://doi.org/10.20900/agmr20260018
Blood. 2026 Aug 24. pii: blood.2026034204. [Epub ahead of print]

Ferroptotic stress promotes hematopoietic stem cell aging through S1P-dependent epigenetic and lipid remodeling.

Yijun Zhao, Yishan Li, Xiaobin Tian, Jingjing Guan, Yixin Ma, Xiaoqi Wang, Hongjian Zhang, Kaitao Wang, Kaizheng Jiang, Yalan Yang, Yuan Pan, Weiwei Liu, Xianzhe Hu, Jiafan Cao, Weiming Liu, Mengyun Xie, Kexin Sun, Jiayin Zheng, Ying Wang, Yucan Zheng, Yanjun Ling, Keyue Yang, Xuying Pei, Xiang-Yu Zhao, Xi Zhang, Pengxu Qian, Changzheng Li, Tian Lan, Linjia Jiang, Meng Zhao.

Aging of hematopoietic stem cells (HSCs) impairs hematopoietic regeneration and differentiation, contributing to immune aging, systemic inflammation, and reduced lifespan. Strategies to rejuvenate aged HSCs and restore immune homeostasis remain limited. Here, we identify ferroptotic stress as a key contributor to HSC aging. Mechanistically, increased sphingosine metabolism elevates sphingosine-1-phosphate (S1P), which suppresses HDAC activity and enhances H3K9 acetylation to upregulate lysophosphatidylcholine acyltransferase 2 (Lpcat2), thereby promoting the accumulation of pro-ferroptotic phospholipids in aged HSCs. Genetic or pharmacological inhibition of sphingosine kinase 2 (Sphk2) reduces S1P levels, suppresses Lpcat2 expression, and attenuates ferroptotic stress in aged mouse and human HSCs. Notably, Sphk2 inhibition improves HSC function, restores immune homeostasis, and modestly extends lifespan in aged mice. Together, these findings identify an S1P-HDAC-Lpcat2 pathway linking epigenetic and lipid remodeling to ferroptotic stress and highlight sphingosine metabolism as a therapeutic target for HSC aging.

DOI: https://doi.org/10.1182/blood.2026034204
Blood. 2026 Aug 25. pii: blood.2026033244. [Epub ahead of print]

Inhibition of nucleoporin 214 depletes leukemia stem cells by promoting heme catabolism and lipid peroxidation.

Zhe Chen, Feng Wu, Wei Zhang, Wei Guo, Yan Li, Qiang Gong, Yue Wei, Linfeng Li, Tao Chen, Xueya Zhao, Jianwen Xiao, Hanqing Zeng, Jianchuan Deng, Hua-Bing Li, Li Wang, Zufeng Guo, Yu Hou.

Chromosomal translocations involving nucleoporin (NUP) loci, such as NUP98 and NUP214, are recurrent in acute myeloid leukemia (AML). However, the intrinsic functions of wild-type nucleoporins in AML remain largely unknown. By screening the NUP family, we identified NUP214 as a frequently overexpressed gene and a critical fitness determinant in leukemia stem cells (LSCs). NUP214 acts as a conserved driver of LSC survival by restricting heme catabolism, limiting Fe²⁺ accumulation, and suppressing lipid peroxidation. Conversely, NUP214 deficiency leads to upregulation of heme oxygenase 1 (HMOX1) and arachidonate 15-lipoxygenase (ALOX15), causing heme exhaustion and excessive lipid peroxidation, which ultimately triggers ferroptosis in LSCs and impairs AML progression. Mechanistically, NUP214 translocates into the nucleoplasm where it blocks Sub1-mediated RNA polymerase II recruitment to repress transcription of the key pro-ferroptotic genes HMOX1 and ALOX15, revealing a non-canonical role beyond its nuclear pore function. Furthermore, we developed the small-molecule compound 0449-b, which acts as a selective NUP214 degrader by recruiting NUP214 to the Cullin5-Rbx2 E3 ligase complex, inducing its neddylation and proteasomal degradation. 0449-b potently triggers LSC ferroptosis and exhibits anti-leukemic activity in vivo, while sparing normal hematopoietic stem cells. Collectively, our findings establish NUP214 as a critical oncoprotein that orchestrates heme metabolism and lipid peroxidation to sustain LSCs, and highlight NUP214-targeted degradation as a promising intervention strategy for AML.

DOI: https://doi.org/10.1182/blood.2026033244
Stem Cell Reports. 2026 Aug 27. pii: S2213-6711(26)00270-5. [Epub ahead of print] 103059

Bone marrow-inspired DLL1-presenting microparticles enhance asymmetric division and maintenance of mouse hematopoietic stem and progenitor cells.

Li Wenjing, Feng Yiting, Han Dongbo, Ao Yanxiao, Michael W Chen, Li Ning, Jin Yuhong, Liang Haiwei, Liu Wen, Zhu Xiaoyu, Du Yanan.

  Understanding the regulation of hematopoietic stem and progenitor cell (HSPC) fate and translating it into effective culture strategies remains a significant challenge. Asymmetric lysosomal inheritance during HSPC division has been shown to predict variations in daughter cell activity and fate, yet the underlying regulators remain unclear. Through cell-cell communication analysis of bone marrow single-cell sequencing data, we identified the Notch ligand Delta-like protein 1 (DLL1) as a potential regulator in HSPC asymmetric division (ACD). Interactions between DLL1-presenting microparticles (MP-Ds) and HSPCs were observed in addressable microwell arrays, simulating cellular responses to localized niche signals. Long-term single-cell tracking revealed that MP-D interactions polarized HSPC lysosomes toward the contact site, directing division orientation and consequent asymmetric lysosomal inheritance in paired daughter cells. Furthermore, this co-culture system enhanced long-term hematopoietic reconstitution capacity of HSPCs in serial transplantations. Our findings support an association between HSPC ACD and the presentation mode of DLL1 signals, which enhances the ex vivo maintenance of HSPCs.

Keywords:  DLL1; Delta-like protein 1; asymmetric division; bone marrow niche; hematopoietic stem cells; microparticles

DOI:  https://doi.org/10.1016/j.stemcr.2026.103059
Nat Commun. 2026 07 28. pii: 9133. [Epub ahead of print]17(1):

Clonal memory of cell division in humans diverges between healthy haematopoiesis and acute myeloid leukaemia.

Alessandro Donada, Gurvan Hermange, Tiziana Tocci, Adil Midoun, Giulio Prevedello, Louisa Hadj Abed, Délia Dupré, Wenjie Sun, Idan Milo, Sabrina Tenreira Bento, Constandina Pospori, Andrew J Innes, Christophe Willekens, Jacques Vargaftig, David Michonneau, Cristina Lo Celso, Nicolas Servant, Ken R Duffy, Hervé Isambert, Paul-Henry Cournède, Lucie Laplane, Leïla Perié.

Clonal memory, a cellular property inherited across at least two divisions, is a key driver of cell heterogeneity. To uncover its roles in human haematopoiesis, we develop high-resolution ex vivo tools that track both division and fate commitment of individual primary human haematopoietic stem and progenitor cells (HSPCs). We show that human HSPCs display a clonal memory of division, as cells descending from the same ancestor cell divide synchronously over multiple generations. In parallel, HSPCs inherit a clonal memory of fate commitment, independently of lineage identity. Both forms of clonal memory persist over at least two divisions, across different HSPC commitment stages and cell culture conditions. In contrast, malignant haematopoiesis exhibits lower synchronicity, revealing a disruption of clonal memory in leukaemic cells. Epigenetic remodelling using a bromodomain inhibitor partially restores the clonal memory in division in leukaemic HSPCs, highlighting the plasticity of this trait and its potential for therapeutic modulation. Our findings position clonal memory as a key regulator of human haematopoietic stem cell behaviour. Demonstrating that clonal memory can be modulated opens avenues for tuning cell heterogeneity in healthy and pathological tissues.

DOI: https://doi.org/10.1038/s41467-026-75250-y
Leukemia. 2026 Aug 27.

Cheminformatic identification of small molecules targeting acute myeloid leukemia.

Megan R Daneman, Bernadetta Meika, Lois Armendariz, Elissa Tjahjono, Alexey V Revtovich, Leonid A Stolbov, Natthakan Thongon, Natalia Baran, Scott R Gilbertson, Vladimir V Poroikov, Natalia V Kirienko.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor prognosis and high relapse rates when treated with cytotoxic chemotherapeutics. Previously, we identified a family of small molecules that modulate mitochondrial function, referred to as PS127-family compounds. These drugs were selectively toxic to AML and were characterized by two predicted functions: apoptotic agonism and thioredoxin/glutathione reductase inhibition. Here, we uncovered a third critical predicted function, autophagic induction. Using a cheminformatic screen of ~4.2 million compounds for molecules with high predicted probability for all three functions, we found and validated hits that selectively killed AML cells, activated apoptosis, were dependent upon autophagic activation, and compromised glutathione metabolism by interfering with glutathione reductase, all of which are consistent with predictions. Compound treatment increased pools of cytosolic and mitochondrial ROS, decreased oxygen consumption, and reduced ATP synthesis. Structurally unrelated compounds caused the same phenotypes, validating our approach of screening for predicted function. Finally, we also observed strong synergy between these compounds and midostaurin and venetoclax, underscoring their therapeutic potential. Key phenotypes, including the compounds' impact on glutathione metabolism and synergy with doxorubicin and midostaurin, were confirmed in AML-patient-derived primary cells, validating the potential of these compounds for the development of future AML treatments.

DOI: https://doi.org/10.1038/s41375-026-03104-z
Semin Immunol. 2026 Aug 25. pii: S1044-5323(26)00042-4. [Epub ahead of print]83 102055

IL-1-mediated cancer-adapted hematopoiesis in aging and clonal hematopoiesis.

Francisco Caiado, Nagihan G Gonullu, Markus G Manz.

  A defining and evolutionary-selected feature of hematopoiesis is its capacity to adapt to organismal cellular needs. This demand-adapted hematopoiesis relies on a complex peripheric immune system capable of sensing minute amounts of damage and pathogen molecular patterns and trigger an inflammation-based reaction that sets the organism on alert. At a receiver-end of this response are bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) which rapidly sense inflammatory messages and engage in differentiating divisions to replenish the consumed innate immune cells, bringing the organism back into homeostasis. Cancer can elicit such systemic inflammatory-immune response, possibly as an initial attempt to contain tumor progression, which pushes HSPC differentiation towards myeloid cells production (myelopoiesis) in a process here termed cancer-adapted hematopoiesis (CAH). CAH leads to proliferation and mobilization of HSPCs, causing extramedullary hematopoiesis (EMH) and increased myelopoietic output that, due to its accelerated nature, generates immature myeloid cells with immunosuppressive functions that support tumor progression, generally termed myeloid-derived suppressor cells (MDSC). While multiple inflammatory pathways are implicated in CAH, here we focus on the impact of IL-1 pathway, which is a well-established modulator of HSPC biology in contexts of sterile inflammation, infection and myeloablation. We present evidence for the IL-1 pathway as a central driver of CAH acting both as a direct and indirect agent between tumors and HSPCs. Moreover, we highlight recent models on how IL-1-mediated CAH is impacted by age and clonal disorders of the hematopoietic system, further highlighting its pathological and thus targetable role in cancer progression.

Keywords:  Age; Cancer; Clonal Hematopoiesis; Extramedullary Hematopoiesis; Hematopoiesis; Hematopoietic Stem Cell; Inflammation; Interleukin-1; Tumor; Tumor Microenvironment

DOI:  https://doi.org/10.1016/j.smim.2026.102055
Mol Ther Adv. 2026 Sep 10. 34(3): 201799

Engineering hematopoietic stem and progenitor cells to generate red blood cells as viral traps against HIV-1.

Sofia E Luna, William N Feist, Kaya Ben-Efraim, Alex Pendergast, Freja K Ekman, Britney Hernandez-Naughton, Megan Merritt-Garza, Kathleen Romero, Zak Kostamo, Nelson A Amorin, Nicole M Johnston, Hana Y Ghanim, Vivien Sheehan, Amanda M Dudek, Matthew H Porteus.

  Canonical HIV-1 entry into target cells depends on binding to CD4 as a primary receptor. Because of this, use of the CD4 receptor as a viral trap (a decoy receptor used to prevent infection of target cells) is a promising strategy for the treatment of HIV-1. One challenge in using CD4 viral traps is maintaining enough of the decoy receptor in circulation to remain effective. Here, we present a strategy to produce cell-based CD4 viral traps by engineering hematopoietic stem and progenitor cells (HSPCs) to express the CD4 receptor in red blood cell (RBC) progeny. This takes advantage of the ability of the HSPC to repopulate the blood system for a lifetime, while leveraging the fact that RBCs greatly outnumber any cell targeted for infection. CRISPR-Cas9-engineered HSPCs efficiently express CD4 on their cell surface after differentiation to the RBC lineage in vitro. Fusion of CD4 to glycophorin A (GPA) and introduction of a truncated erythropoietin receptor (tEPOR) leads to increased CD4 expression and enrichment of edited cells (CD4-GPA-tEPOR) to levels capable of neutralizing HIV-1 pseudovirus in vitro. In sum, this work presents a potential strategy for the one-time delivery of CD4-RBC viral traps through autologous transplantation of engineered HSPCs.

Keywords:  CD4; CRISPR/Cas9; HIV-1; genome-editing; hematopoietic stem cell; hematopoietic stem cell transplant; homology directed repair; red blood cell; viral trap

DOI:  https://doi.org/10.1016/j.omta.2026.201799
BioTech (Basel). 2026 Aug 05. pii: 63. [Epub ahead of print]15(3):

Differential Correlation Across Subpopulations of Single Cells in Subtypes of Acute Myeloid Leukemia.

Reginald L McGee, Jake Reed, Gregory K Behbehani, Kevin R Coombes.

  Mass cytometers can record 40-50 parameters per single cell for millions of cells in a sample. Many methods have been developed to cluster phenotypically similar cells within cytometry data, but there are fewer methods to visualize activity and interactions of pairs of proteins across these populations. We have developed a workflow for analyzing correlations associated with predefined populations. By clustering blood samples from acute myeloid leukemia (AML) patients and normal controls using an established algorithm, we obtained a minimum spanning tree of clusters of single cells. Using surface marker expression, we identified clusters on the tree that belonged to phenotypes of interest. Next, we computed correlations between pairs of proteins in each cluster. We developed a novel, coherent, probability-based statistic to test differences between vectors of correlation coefficients. By comparing all combinations of the normal controls under the statistic, we created an empirical distribution that could provide a conservative threshold of differential correlation. Using this empirically derived distribution to define significance, we compared pooled samples from AML subtypes and normal controls to detect differential correlations. Given the structure present within this cytometry dataset, we found it natural to consider correlations in this manner versus aggregating all data and computing a single correlation. Our approach has the advantage that we can localize the statistical measure to determine contributions from particular phenotypic populations. Differentially correlated pairs of proteins can be further explored as possible testable hypotheses by considering a population's distribution of correlation coefficients or biaxially plotting protein expressions within individual cells in a given population.

Keywords:  acute myeloid leukemia; correlations in context; differential correlation; mass cytometry

DOI:  https://doi.org/10.3390/biotech15030063
Leukemia. 2026 Aug 24.

PTBP1 controls oncogenic transcript processing and maintenance of acute myeloid leukemia.

Zhendong Cao, Kurtis N McCannell, Sixiang Yu, Krista A Budinich, Won Jun Kim, Yuqing Jing, Michelle Y Wang, Steven Tittley, Zhuoyu Wen, Kathy Fange Liu, Junwei Shi, Omar Abdel-Wahab.

RNA-binding proteins are critical regulators of gene expression in both normal physiology and cancer. Here we set out to systematically annotate the functions of RNA-associated proteins across multiple cancer types via domain-focused CRISPR screens targeting RNA-modifying enzymes and RNA-binding proteins. We utilized 3182 sgRNAs targeting 527 RNA-enzymatic and binding domains in 341 RNA-associated proteins and identified multiple RNA-binding proteins as dependencies in acute myeloid leukemia (AML), including the RNA splicing factor PTBP1 and the N6-methyladenosine reader RBM15, with a bias toward the aggressive KMT2A-rearranged (KMT2A-r) subtype of AML. Genetic and cellular validation confirmed all four RNA-binding domains of PTBP1 as required for KMT2A-r AML proliferation. In contrast to the lack of requirement for PTBP1 in myelopoiesis, PTBP1 suppression in AML caused cell cycle arrest, apoptosis, and induction of myeloid differentiation programs. Transcriptomic analysis revealed that PTBP1 loss disrupted the KMT2A-r-essential transcriptional program and caused widespread dysregulation of splicing. CLIP-seq analysis further identified that PTBP1 preferentially binds to a subset of transcripts critical for KMT2A-r AML proliferation, including IKZF1, MEF2C, EZH2, SIK3, and PBX3. Collectively, these findings demonstrate that PTBP1 supports AML proliferation by fine-tuning the expression and splicing of AML-essential genes, providing a workflow for systematically annotating RNA-associated protein dependencies in cancer.

DOI: https://doi.org/10.1038/s41375-026-03098-8
Exp Hematol. 2026 Aug 27. pii: S0301-472X(26)00506-0. [Epub ahead of print] 105873

Evolution in the cryopreservation of hematopoietic stem cells.

Krishna Patel, Victoria E Siltamäki, Robert N Ben, Nicolas Pineault.

  Hematopoietic stem cells (HSCs) are essential for the reconstitution of the hematopoietic and immune systems and are widely used in transplantation and emerging cell-based therapies. Cryopreservation is a critical technology enabling long-term storage, banking, and distribution of HSC grafts and immuno-oncology cell products. However, the cryopreservation process exposes stem cells and progenitors to multiple sources of cryoinjury, including intracellular ice formation, osmotic shock, solute effects and ice recrystallization, which can compromise post-thaw viability, recovery and functional potency. For decades, dimethyl sulfoxide (DMSO) has remained the gold-standard cryoprotective agent (CPA) due to its ability to reduce osmotic stress, limit intracellular ice formation and stabilize cellular structures. Despite its widespread use, it is associated with dose- and time-dependent cytotoxicity and adverse infusion-related reactions, motivating efforts to reduce or replace its use. This review summarizes key cryobiological principles underlying HSC preservation, including the importance of optimized CPA exposure, controlled cooling, rapid thawing, and storage below glass transition temperature. We also discuss established and emerging permeating and non-permeating CPAs, including sugars, polymers, and carbohydrate-based ice recrystallization inhibitors (IRI), several of which have shown to improve post-thaw outcomes and engraftment in preclinical models. Finally, we review strategies to mitigate DMSO toxicity, including reduced-DMSO formulations and newly developed "all-in-one" DMSO-free cryosolutions. Collectively, these advances are driving the evolution of safer and more effective cryopreservation strategies for HSC transplantation and next-generation cellular therapeutics.

Keywords:  DMSO-free cryosolutions; cryopreservation; cryoprotectants; hematopoietic stem cells; ice recrystallization; transient warming events

DOI:  https://doi.org/10.1016/j.exphem.2026.105873
Life Sci Alliance. 2026 Nov;pii: e202603746. [Epub ahead of print]9(11):

Single-cell chromatin profiling reveals relapse-related priming in pediatric acute myeloid leukemia.

Boyu Cui, Minghui Lei, Liwei Liu, Mingxin Shu, Furong Yu, Kai Yang, Yin Pan, Yunhong Song.

Relapse remains the leading cause of treatment failure and mortality in pediatric acute myeloid leukemia (pAML), yet the early molecular features underlying relapse susceptibility remain poorly understood. Here, we leveraged our previously generated single-cell chromatin accessibility dataset comprising 177,500 cells from 16 diagnostic pAML samples with long-term clinical outcome data, spanning t(8;21), inv(16), and FLT3-ITD subtypes and stratified into relapse (RPS) and non-relapsed (NRPS) cases. We show that RPS patients harbor relapse-associated chromatin accessibility signatures already detectable at diagnosis across multiple molecular subtypes. These patients display heightened innate immune and inflammatory activation and expansion of HSC/MPP-like leukemic progenitors with stem cell-like regulatory features. Motif enrichment analyses identify AP-1 family members, together with RUNX1, SPI1, and ETS factors, as central regulators shaping the relapse-associated epigenetic state. Elevated expression of these regulators predicts inferior survival across independent AML cohorts. Collectively, these findings suggest that early epigenetic priming of innate immune and inflammatory programs is associated with a relapse-prone state and highlight this core transcriptional network as a candidate biomarker framework in pAML.

DOI: https://doi.org/10.26508/lsa.202603746
Stem Cell Rev Rep. 2026 Aug 24.

Maternal and Neonatal Factors Impacting the Volume and Cellular Composition of Umbilical Cord Blood.

Yu Li, Jia Liu, Ming Li, Chunyu He, Bin Guo, Ye Yang, Rongzhen Jiang.

   BACKGROUND: Umbilical cord blood (UCB) is a well-established source of hematopoietic stem cells (HSCs) for transplantation, with over 30 years of clinical experience confirming its safety and efficacy. However, the limited cell count contained for a single UCB unit remains a major constraint on its application in adult recipients, and donor eligibility criteria vary greatly among different cord blood banks.
OBJECTIVE: This study aimed to identify key maternal, neonatal, and perinatal factors that influence the volume and quality of collected UCB to help overcome this limitation.
METHODS: We conducted a retrospective analysis of 229 UCB units voluntarily donated by pregnant women at our hospital. Correlations between UCB parameters and a range of clinical characteristics were evaluated.
RESULTS: Maternal body mass index (BMI), umbilical cord length, and UCB oxygen partial pressure (pO2) were independently associated with UCB volume and cellular parameters. Furthermore, umbilical cord length and maternal platelet-to-lymphocyte ratio (PLR) showed associations with TNC count in univariate analysis, although no independent factors were identified after multivariable adjustment. The CD34+/TNC ratio was independently associated with umbilical cord length, gestational age, maternal total cholesterol level, placental weight, and UCB pH value. Finally, umbilical cord length was independently associated with the total CD34+ cell count.
CONCLUSION: These findings provide preliminary evidence that selected maternal, neonatal, and perinatal characteristics are associated with UCB volume and cellular parameters. Further multicenter studies incorporating functional stem-cell assessments and transplantation outcomes are required before changes to donor eligibility or UCB unit-selection criteria can be considered.

Keywords:  Cord blood; Cord blood stem cells; Maternal-neonatal factors

DOI:  https://doi.org/10.1007/s12015-026-11205-6
Blood Adv. 2026 Aug 25. pii: bloodadvances.2026021669. [Epub ahead of print]

Interpreting cord blood transplant outcomes in BMT CTN 1702.

Rajdeep Das, Andromachi Scaradavou, Juliet Barker, Warren B Fingrut.

DOI: https://doi.org/10.1182/bloodadvances.2026021669
J Inherit Metab Dis. 2026 Sep;49(5): e70236

From Single Cells to Diagnosis: Proteomics Technologies in the Multi-Omics Landscape of Rare and Mitochondrial Diseases.

Simon Wetzel, Sebastian Porsdam Mann, Florian A Rosenberger.

  Proteomics by mass spectrometry has rapidly matured from a niche method into a standard tool. The recent 10-year trajectory of single-cell proteomics has opened a new biological dimension for studying disease. Mitochondrial diseases, with their pronounced cell-to-cell heterogeneity, are particularly, well-suited to these methods. Here, we discuss how this approach can serve as an orthogonal functional layer for rare disease diagnostics. We trace the evolution of rare disease diagnostics from biochemical enzyme assays through genomics, transcriptomics, proteomics and metabolomics, highlighting incremental gains in diagnostic yield from individual omics layers and their integration. We discuss the limitations of bulk approaches in capturing the functional consequences of genetic perturbations, the new opportunities opened up by single-cell measurements and how spatial single-cell proteomics can further enrich the biological signal of affected cells in diagnostic tissues. We observe that the persisting diagnostic gap reflects not only technological limitations but, increasingly, challenges in data sharing and infrastructure as well as interpretive frameworks for functional molecular evidence. In this context, we consider opportunities for artificial intelligence and the ethical dimensions of single-cell proteomics in rare disease diagnostics. Finally, we propose a single-cell deep visual proteomics (scDVP) framework for clinical diagnostics of rare diseases with cell-to-cell variability, arguing that mitochondrial diseases are an ideal proof-of-concept.

Keywords:  diagnostics; mitochondria; omics ethics; rare diseases; single‐cell proteomics; spatial proteomics

DOI:  https://doi.org/10.1002/jimd.70236
PLoS Biol. 2026 Aug 26. 24(8): e3003953

Dynamic Landscape Analysis of cell fate decisions provides predictive models of neural development from single-cell data.

Marine Fontaine, M Joaquina Delás, Meritxell Sáez, Rory J Maizels, Elizabeth Finnie, James Briscoe, David A Rand.

Building a mechanistic understanding of cell fate decisions remains a fundamental goal of developmental biology, with implications for stem cell therapies, regenerative medicine and understanding disease mechanisms. Single-cell transcriptomics provides a detailed picture of the cellular states observed during these decisions, but building dynamic and predictive models from these data remains a challenge. Here, we present dynamic landscape analysis (DLA), an integrative framework that applies dynamical systems theory to identify stable cell states, map transition pathways, and generate a predictive cell fate decision landscape from single-cell data. Applying this framework to vertebrate neural tube development revealed that progenitor specification by Sonic Hedgehog (Shh) can be captured in a landscape with an unexpected topology in which initially divergent lineages converge to the same fate through multiple distinct routes. The model accurately predicted cellular responses and cell fate allocation for unseen dynamic signalling regimes. Cross-species validation using human embryonic organoid data demonstrated conservation of this decision-making architecture. By modelling the dynamic responses that drive cell fate decisions, the DLA framework provides a quantitative and generative framework for extracting mechanistic insights from high-dimensional single-cell data.

DOI: https://doi.org/10.1371/journal.pbio.3003953
Cell Stem Cell. 2026 Aug 25. pii: S1934-5909(26)00272-9. [Epub ahead of print]

Spatial profiling of the spleen in mouse and human myelofibrosis reveals complement-driven immune-stromal interactions as a therapeutic target.

Bérénice Dugué, Pia Wanner, Mayra L Ruiz Tejada Segura, Mohamed Saad, Lucas Greven, Katrin Götz, Carmen Schalla, Stijn Fuchs, Gerjanne Vroeg In de Wei, Hélène F E Gleitz, Anna Katharina Galyga, Jessica Ellen Pritchard, Tobias Schlangen, Niklas Lutterbach, Salim Atakhanov, Lina Schmidt, Marie Parrens, Armelle Peyrat, Damien Luque Paz, Marie-Christine Copin, Alexandre Guy, Victor-Emmanuel Brett, Olivier Mansier, Susanne Schmitz, Paul Wanek, Bella Banjanin, Stephani Schmitz, Martina Crysandt, Marian C Clahsen-van Groningen, Konnie M Hebeda, Sascha Dietrich, Harald Voehringer, Matthias Meyer-Bender, Kristin Séré, Chloé James, Adam Benabid, Ivan Costa, Charles Dussiau, Rebekka K Schneider.

  Splenomegaly is a defining feature of myelofibrosis, yet the contribution of splenic mesenchymal stroma to disease progression remains unclear. We combined spatial and single-nucleus transcriptomics of patient spleens with spatial and single-cell transcriptomics, as well as imaging analyses, of murine spleens to map extramedullary hematopoiesis niches. Activated red pulp reticular cells localize near hematopoietic stem and progenitor cells, and early disease is characterized by marginal zone disruption with lymphoid depletion preceding stromal remodeling. Trajectory analyses reveal a shift in reticular cells from hematopoiesis-supportive to inflammatory and pro-fibrotic states, driven by macrophage- and megakaryocyte-derived signals that activate complement and induce tumor necrosis factor α (TNF-α), transforming growth factor β (TGF-β), extracellular matrix, and Thbs1 programs. Non-hematopoietic complement component C3 deficiency or pharmacological C3 inhibition suppresses these pathways, restores splenic architecture, and reduces splenomegaly and bone marrow fibrosis. These findings identify complement-dependent stromal reprogramming as a mechanism governing hematopoietic niches and as a targetable axis in myelofibrosis.

Keywords:  complement C3; extramedullary hematopoiesis; fibrosis; hematopoietic stem and progenitor cells; microenvironment; myelofibrosis; reticular cells; splenic stroma; splenomegaly; stromal reprogramming

DOI:  https://doi.org/10.1016/j.stem.2026.07.012
Cell Stem Cell. 2026 Aug 25. pii: S1934-5909(26)00303-6. [Epub ahead of print]

Splenic extramedullary hematopoiesis in myelofibrosis is shaped by transcriptomic and epigenetic dysregulation.

Rebecca Austin, Madeline H Kowalski, Xiaoli Wang, Ziyan Lin, Bettina Nadorp, Nicholas Ward, Pier Edoardo Rovatti, Audrey Lasry, Zhengxi Sun, Julia Rojo-Tomillo, Giovanni Gambi, Tejas Patel, Hua Zhou, M D Babu Mia, Eduardo Esteva, Igor Dolgalev, Valeria Mezzano, Suhita Ray, Sergei Doulatov, Tatyana Gindin, Sanam Loghavi, Bethan Psaila, Aristotelis Tsirigos, Rahul Satija, Iannis Aifantis, Ronald Hoffman.

  Myelofibrosis (MF) is a chronic, progressive myeloproliferative neoplasm characterized by bone marrow fibrosis, ineffective blood cell production, and neoplastic extramedullary hematopoiesis (EMH) occurring primarily within the spleen. To explore the molecular mechanisms underlying splenic EMH, we performed single-cell transcriptional and chromatin profiling of cells from MF spleens that had been surgically removed. We demonstrate significant expansion of hematopoietic stem and progenitor cells, coupled with aberrant differentiation toward the erythroid and megakaryocytic lineages, associated with a significant enrichment of inflammatory pathways with enhanced NF-κB signaling and IFN responses, as well as dysregulation of the inferred function of differentiation-defining transcription factors. Finally, we report a significant remodeling of the immune microenvironment in MF spleens, characterized by emergence of dysfunctional T cell subsets and inflammatory memory B cells, suggesting the concomitant establishment of a pro-inflammatory and immune-tolerant tumor microenvironment within the spleen that influences hematopoietic cell differentiation and impairs tumor immune surveillance.

Keywords:  extramedullary hematopoiesis; immune system; inflammation; megakaryocyte; myelofibrosis; spleen

DOI:  https://doi.org/10.1016/j.stem.2026.08.002
Bioinformatics. 2026 Aug 01. pii: btag496. [Epub ahead of print]42(Supplement_2):

usiGrabber: automating the curation of proteomics spectra data at scale, making large datasets ready for use in machine learning systems.

Georg Auge, Matthis Clausen, Konstantin Ketterer, Jacob Schaefer, Nils Schmitt, Tom Altenburg, Yannick Hartmaring, Hendrik Raetz, Christoph N Schlaffner, Bernhard Y Renard.

MOTIVATION: An unprecedented amount of mass spectrometry-based proteomics data is publicly available through repositories such as the PRoteomics IDEntifications Database (PRIDE), and the field is increasingly leveraging machine-learning approaches. However, the available data is not ready to be reused in a scalable way beyond the original acquisition purpose. Existing machine learning models commonly rely on a few manually curated datasets that require deep domain expertise and tedious technical work to construct. Importantly, these datasets have not been updated in recent years, so that newly published data remains inaccessible. We present usiGrabber, a scalable framework for assembling large proteomic datasets. usiGrabber is designed around portability and extensibility. It extracts spectra identification data from mzIdentML files, stores additional project-level metadata retrieved through the PRIDE API, indexes raw spectra using Universal Spectrum Identifiers (USIs), and offers download utilities to retrieve spectra data at scale.
RESULTS: Within 49 h, we parsed over 800 million peptide spectrum matches and corresponding USIs from over 1200 projects. As a proof of concept, we used usiGrabber to construct a phosphorylation-specific training dataset of nearly 11 million spectra in under 2 days and used it to retrain a binary phosphorylation classifier based on the AHLF model architecture. With a balanced accuracy of 0.78, our model achieves comparable performance to the original model on an independent test set, showing that automated data extraction is an alternative to manual curation of static datasets.
AVAILABILITY AND IMPLEMENTATION: All code is available at https://github.com/usiGrabber/usiGrabber; the data are available at https://zenodo.org/records/18853258.

DOI: https://doi.org/10.1093/bioinformatics/btag496