bims-mithem 2025-10-05 papers

Issue of 2025–10–05
four papers selected by
Tim van Tienhoven, Erasmus Medical Center

Annu Rev Cell Dev Biol. 2025 Oct;41(1): 231-258

Regulation of Hematopoietic Stem Cell Dormancy and Quiescence: Insights into Regeneration and Disease.

Jasmin Rettkowski, Nina Cabezas-Wallscheid.

Stem cells are undifferentiated cells capable of self-renewal and differentiation into specialized cell types, forming the foundation of tissue maintenance and repair. In the blood system, this process is known as hematopoiesis. Hematopoietic stem cells (HSCs), positioned at the apex of the hematopoietic hierarchy, have the unique ability to reconstitute the hematopoietic system long-term. HSC stemness is defined by multipotency, allowing differentiation into all blood lineages, and self-renewal, maintaining the stem cell pool. A fundamental property of HSCs is quiescence, which refers to a reversible inactive cell cycle state that preserves their self-renewal potential. Dormant HSCs represent a subset of quiescent stem cells with minimal division rates and the most potent stemness. Dysregulation of dormancy and quiescence is linked to HSC dysfunction. Here, we explore mechanisms regulating HSC dormancy and quiescence under homeostatic and stress conditions. Finally, we describe how factors such as aging, inflammation, and malignancies disrupt these states.

Keywords: dormancy; hematopoiesis; hematopoietic stem cells; molecular mechanisms regulating hematopoietic stem cells; quiescence; stem cell exhaustion

DOI: https://doi.org/10.1146/annurev-cellbio-101323-023806

Mol Biol Rep. 2025 Sep 30. 52(1): 971

Exploring the connection between the Mitochondrial DNA and the Circadian Rhythm: Insights into Mitochondrial Biogenesis and its Dynamics.

Sowmya Anand, Piyush Jagdish Balgote, Jayanthi Sivaraman.

Mitochondrial DNA (mtDNA), inherited exclusively from the mother, encodes genes essential for mitochondrial function, including oxidative phosphorylation (OXPHOS), which generates ATP, the cell's primary energy currency. Circadian rhythm is a crucial biological system that refers to the innate biological clock, whose core is in the suprachiasmatic nucleus (SCN) of the brain. This nucleus regulates various physiological processes, such as sleep-wake cycles, hormone secretion, cellular repair, energy homeostasis, and metabolism, on a roughly 24-hour cycle. Peripheral clocks exist in various tissues, including cells sensitive to external stimuli, and are linked to the circadian rhythm due to mitochondria's role in cellular energy metabolism. Core clock genes like Bmal1 and Clock influence mitochondrial biogenesis, oxidative phosphorylation, and mitophagy, while mitochondrial dysfunction disrupts circadian rhythms, leading to metabolic imbalance and disease progression. Emerging research suggests a bidirectional connection between circadian regulation and mitochondrial dynamics. This review focuses on the complex interplay between the circadian rhythm and mitochondrial processes, as regulated by various cellular proteins, transcription factors, ions, receptors, channels, and the mitochondrial genetic machinery, to understand the harmonious coordination between energy metabolism and timing mechanisms needed to optimize cellular processes and maintain physiological balance. The study of this relationship provides new insights into aging, neurodegenerative disorders, and metabolic diseases, potentially guiding future interventions focusing on chronotherapy and mitochondrial targeting.

Keywords: BMAL1; Circadian rhythm; Mitochondrial DNA (mtDNA); Mitochondrial biogenesis; PGC1-α; SIRT

DOI: https://doi.org/10.1007/s11033-025-11010-3

Curr Stem Cell Res Ther. 2025 Sep 25.

Revisiting Hematopoietic Hierarchy: Emerging Insights into Megakaryocyte-Biased Differentiation Pathways of Hematopoietic Stem Cells.

Ai Gao, Yuemin Gong.

Hematopoietic stem cells (HSCs) represent the most primitive cell population endowed with the ability for self-renewal and differentiation. They possess the capacity to differentiate into all types of blood cells, each serving unique functions. Traditional theories have established a clear hierarchical relationship between HSCs, their progenitors, and mature blood cells. The identification of distinct cell populations within the hematopoietic system forms the foundation of the hematopoietic differentiation model. However, recent research has led to a constant evolution of our understanding of the hierarchical structure of hematopoietic differentiation, particularly in the context of megakaryocyte differentiation pathways. Megakaryocytes are essential for platelet production, a critical process in hemostasis and thrombosis. Understanding the mechanisms underlying megakaryocyte-biased HSCs differentiation holds significance for both basic research and clinical applications. In this review, we consolidate the latest research progress concerning the evidence supporting these nonclassical pathways of megakaryocytic differentiation. Furthermore, we delve into the alterations observed in these pathways under conditions of steady state, transplantation, stress, and aging.

Keywords: Hematopoietic stem cell; megakaryocyte; platelet.

DOI: https://doi.org/10.2174/011574888X395136250908045533

Am J Physiol Heart Circ Physiol. 2025 Sep 30.

MitoQ reduces senescence burden in Doxorubicin-treated endothelial cells by reducing mitochondrial ROS and DNA damage.

Hossein Abdeahad, Denisse G Moreno, Samuel Bloom, Lucas Norman, Lisa A Lesniewski, Anthony J Donato.

Cardiovascular toxicity is one of the adverse consequences of chemotherapy, limiting its therapeutic application. Chemotherapeutics, such as doxorubicin (DOXO), induce endothelial dysfunction via genotoxic effects, and reactive oxygen species (ROS) and mitochondrial ROS (mtROS) generation. These mechanisms increase DNA damage and cellular senescence, a persistent cell cycle arrest promoting inflammation, which elevates future cardiovascular disease risk. The adverse impact of DOXO on endothelial function can be mitigated by the mitochondria-targeted antioxidant, MitoQ; however, its precise protective mechanism in endothelial cells (ECs) remains unclear. The present study hypothesizes that co-treating ECs with MitoQ and DOXO attenuates DOXO-induced mtROS, thereby reducing DNA damage, senescence, and inflammation. Mitochondrial superoxide levels, mitochondrial mass, DNA damage, and cellular senescence were assessed in human umbilical vein ECs (HUVECs) 48 hours after DOXO and/or MitoQ treatment. DOXO treatment increased mtROS production and reduced mitochondrial mass compared to the vehicle group. Co-treatment with MitoQ decreased mtROS production and preserved mitochondrial mass compared to DOXO alone. MitoQ Co-treatment prevented senescence induction in DOXO-treated HUVECs, evidenced by preventing increased mRNA expression for senescence markers and senescence-associated beta-galactosidase (SA-ꞵgal) activity, alongside higher cell proliferation (BrdU incorporation). Additionally, MitoQ co-treatment reduced DNA damage and telomere dysfunction (DNA damage signaling at telomeres) compared to DOXO alone. Collectively, these data suggest mtROS drives cellular senescence in ECs through increased DNA damage and telomere dysfunction. These findings provide insight into mechanisms underlying DOXO-induced endothelial dysfunction and support mitochondrial-targeted antioxidant treatment as a potential therapeutic to mitigate chemotherapy-induced cardiovascular toxicity.

Keywords: Cardiovascular toxicity; Doxorubicin; Endothelial cell senescence; MitoQ; Mitochondrial ROS

DOI: https://doi.org/10.1152/ajpheart.00568.2025