bims-mazytr 2025-07-06 papers

bims-mazytr

Biomed News

on Maternal‐to‐zygotic transition

Issue of 2025–07–06
eleven papers selected by
川一刀

Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos.
Nucleosome organization of mouse embryos during pre-implantation development.
Expression of LINE-1 elements is required for preimplantation development and totipotency.
Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos.
Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells.
The hierarchical folding dynamics of topologically associating domains during early embryo development.
Intermediate Filament Protein BFSP2 Controls Spindle Formation via HSC70-Mediated Stabilization of CLTC During Oocyte meiosis.
An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal-embryonic signaling.
Mapping single-cell rheology of ascidian embryos in the cleavage stages using AFM.
A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.
Cell type and cell signalling innovations underlying mammalian pregnancy.

Nat Commun. 2025 Jul 01. 16(1): 5630

Echs1-mediated histone crotonylation facilitates zygotic genome activation and expression of repetitive elements in early mammalian embryos.

Yong-Feng Wang, Yu-Ting Wan, Qian-Rong Qi, Qing Tian, Xin-Mei Liu, Qing-Zhen Xie, Ying Yin, Li-Quan Zhou.

Histone crotonylation, a conserved post-translational histone modification, plays a crucial role in transcriptional regulation. However, its function in early embryonic development remains largely unexplored. Here, we perform genome-wide mapping of histone crotonylation in mouse and human early embryos. Our analysis reveals that histone crotonylation is highly enriched at promoter regions and exhibits distinct dynamic patterns throughout embryogenesis. Notably, strong histone crotonylation signals are observed at the mouse 2-cell and human 4-to-8-cell stages, coinciding with zygotic genome activation. In mice, Echs1 knockdown in oocytes, which suppresses histone crotonylation, results in developmental arrest at the 2-cell stage. Further investigation demonstrates that reduced histone crotonylation impairs transcriptional activity at zygotic genome activation genes, retrotransposon elements, and ribosomal DNA loci. Moreover, early embryos from aged female mice exhibit significantly diminished histone crotonylation, while supplementation with exogenous sodium crotonate enhances blastocyst formation. Collectively, our findings establish histone crotonylation as a key regulatory mechanism in early mammalian embryogenesis by facilitating transcriptional activation of zygotic genome activation genes and repetitive elements.

DOI: https://doi.org/10.1038/s41467-025-60565-z
Sci Rep. 2025 Jul 01. 15(1): 21894

Nucleosome organization of mouse embryos during pre-implantation development.

Jitao Zeng, Xiaojuan Tu, Siming Qu, Xichan Chen, Ying Wang, Xiaona Liu, Enchuan Kang, Yi Tian, Qianming Xiang, Binbin Lai, Weiwu Gao, Bing Ni, Wei He.

  Sexual reproduction begins with sperm-oocyte fusion to form a zygote, where chromatin undergoes dramatic reorganization to establish totipotency. Although nucleosomes- the basic units of eukaryotic chromatin and key epigenetic regulators- are extensively remodeled during early embryogenesis, their dynamic repositioning mechanisms and biological implications remain unclear. Here, we employed single-cell MNase sequencing (scMNase-seq) to map genome-wide nucleosome positioning and chromatin accessibility in individual mammalian embryos. We found that nucleosome positioning mirrored somatic cell patterns until the 4-cell stage, with nucleosome depletion and phasing at CTCF sites not fully established until morula formation. By integrating H3K4me3 localization and transcriptomic data, we revealed that nucleosome sparsity at transcription start sites (TSS) and flanking regions correlated with expression levels of genes critical for preimplantation development. Notably, these nucleosome-depleted regions likely serve as regulatory hubs influencing histone modification dynamics. Our study systematically delineates nucleosome reorganization principles during mammalian embryogenesis and provides a high-resolution resource for understanding chromatin remodeling in early development.

Keywords:  Chromatin organization; Embryos; H3K4me3; Nucleosome position; scMNase-seq

DOI:  https://doi.org/10.1038/s41598-025-05642-5
Genes Dis. 2025 Sep;12(5): 101555

Expression of LINE-1 elements is required for preimplantation development and totipotency.

Ru Ma, Nan Xiao, Na Liu.

  Transposable elements, long considered genomic intruders, have been found to play significant and intriguing roles during early embryonic development based on the paradigm shift that has undergone in recent years. Long interspersed element-1 (LINE-1) is the predominant class of retrotransposons with autonomous retrotransposition capabilities in mammals and has emerged as a crucial element of preimplantation development. In this review, we elucidate the expression dynamics of key transposable elements throughout preimplantation development and their contribution to the regulation of developmental progression and totipotency. We also explore the critical function of LINE-1 activation and its rich functional reservoir, which is exploited by the host to provide cis-regulatory elements and functional proteins. Particular highlights of the widespread activities in preimplantation development of LINE-1 during multiple epigenetic modifications such as DNA methylation, histone methylation, ubiquitination, and RNA methylation. The silencing complex and RNA exosome also coordinate with LINE-1 across distinct developmental stages. Accordingly, the up-regulated expression of LINE-1 retrotransposons and their protein products plays a key role in various processes, including the opening of chromatin architecture, zygotic genome activation, aging, and age-related disorders. It may reflect an effect on totipotency and pluripotency of mammalian development. Underscoring its pivotal significance, the nuanced regulation of LINE-1 illuminates its indispensable role in orchestrating the precise coordination essential for the regulation of cellular pluripotency and the intricate mechanisms of zygotic genome activation.

Keywords:  Embryonic stem cells; Epigenetic; LINE-1; Preimplantation development; Totipotent; Transposable elements

DOI:  https://doi.org/10.1016/j.gendis.2025.101555
Development. 2025 Jul 02. pii: dev.204626. [Epub ahead of print]

Deciphering the role of cis-regulatory elements and TFAP2C in the activation of zygotic Sox2 expression in mouse preimplantation embryos.

Jaehwan Kim, Chad S Driscoll, Lijia Li, Catherine A Wilson, Wei Xie, Jason G Knott.

  Cell-fate decisions in preimplantation embryos require the coordinated expression of pluripotency and lineage-specific transcription factors. SOX2 represents the first pluripotency regulator whose expression is restricted to the inside cells of mouse preimplantation embryos. However, the genetic mechanisms that activate the expression of zygotic Sox2 are poorly understood. Here we report that Sox2 expression in mouse embryos is controlled by the actions of key cis-regulatory elements, including a proximal promoter and super enhancer. We show that TFAP2C, a key trophoblast lineage regulator, binds to the Sox2 proximal promoter to activate its expression. Lastly, we provide evidence that TFAP2C and the HIPPO signaling pathway cooperatively regulate Sox2 expression. In summary, this work has important implications in understanding how conventional trophoblast transcription factors, such as TFAP2C, contribute to the activation of early pluripotency genes to facilitate divergent cellular states that support lineage formation.

Keywords:   Sox2 regulatory regions; HIPPO signaling; Pluripotency; Preimplantation embryo; TFAP2C

DOI:  https://doi.org/10.1242/dev.204626
Nat Struct Mol Biol. 2025 Jul 04.

Single-cell long-read Hi-C, scNanoHi-C2, details 3D genome reorganization in embryonic-stage germ cells.

Jiansen Lu, Wen Li, Fuchou Tang.

During mouse development, embryonic-stage germ cells (EGCs) make crucial fate decisions, with female EGCs embarking on meiosis whereas male EGCs enter mitotic arrest until birth. Despite increasing understanding of the reprogramming of epigenetic modifications, the dynamics of three-dimensional (3D) genome structures within individual EGCs remains elusive. Here we present a single-cell input, long-read Hi-C method, termed scNanoHi-C2. We use scNanoHi-C2 to systematically dissect the dynamics of EGC chromatin structures. We find that, despite changes in autosomes similar to spermatogenesis, the X chromosomes of female EGCs show enhanced specific interactions between B compartments. By reconstructing 3D genome models, we observe dynamic chromosome positioning during meiosis, showing that the neighborhood between nonhomologous chromosomes of EGCs is relatively random. Simultaneously, transposable elements undergo dramatic chromatin reorganization and display an asymmetric distribution of Alu/B2 elements around meiotic topologically associated domain boundaries. Moreover, we find that high-order interactions in EGCs at the mitosis stage are mainly enriched in the B compartment, whereas, after the mitosis-to-meiosis transition, enriched high-order interactions shift to refined A compartments, to potentially promote meiotic-specific transcription programs during global genomic condensation. We also reveal an unexpected chromatin structure in mitotic-arrested male EGCs distinct from the previously assumed G0 status, which may prime the unique genome structure for subsequent spermatogenesis. Altogether, our study highlights the potential of scNanoHi-C2 and reveals key features of the chromatin structure reprogramming in EGCs.

DOI: https://doi.org/10.1038/s41594-025-01604-7
BMC Biol. 2025 Jul 01. 23(1): 175

The hierarchical folding dynamics of topologically associating domains during early embryo development.

Xuemei Bai, Xiaohan Tang, Yuyang Wang, Shutong Yue, Xiang Xu, Pengzhen Hu, Jingxuan Xu, Yaru Li, Junting Wang, Huan Tao, Yang Zheng, Bijia Chen, Mengge Tian, Lin Lin, Ruiqing Wang, Yu Sun, Chao Ren, Xiaochen Bo, Hao Li, Hebing Chen, Meisong Lu.

   BACKGROUND: Recent research has indicated a close connection between the three-dimensional (3D) structure of chromatin and early embryo development, with precise higher-order chromatin folding playing a significant role in mediating gene expression. However, the specific role of 3D genomic hierarchical structure and its dynamics in early embryo development remains largely unknown.
RESULTS: In this study, we examined the hierarchical topological association domain (TAD) during early embryo development and its relationship with zygotic gene activation (ZGA), gene expression, and chromatin accessibility to gain a better understanding of the dynamics of TAD nesting levels during this developmental stage. Our findings show that ZGA precedes the establishment of hierarchical TAD, leading to widespread gene expression, an increase in the percentage of high-level TAD structures, and enhanced chromatin accessibility at higher hierarchical levels. Additionally, we utilized a deep neural network to investigate the formation of TAD boundaries and found that histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine trimethylation (H3K27me3) are key features in the establishment of TAD boundaries. Furthermore, we observed heterogeneous dynamics of hierarchical TAD among different species.
CONCLUSIONS: Overall, our study sheds light on the folding dynamics of hierarchical TADs during early embryo development and underscores their close relationship with transcriptional programs.

Keywords:  Deep neural network; Early embryo; Hi-C; Hierarchical TAD

DOI:  https://doi.org/10.1186/s12915-025-02259-y
Adv Sci (Weinh). 2025 Jul 02. e06639

Intermediate Filament Protein BFSP2 Controls Spindle Formation via HSC70-Mediated Stabilization of CLTC During Oocyte meiosis.

Yu Li, Zihao Zhang, Yu Zhang, Bo Xiong.

  As a major component of the cytoskeleton, intermediate filaments are generally considered to play a supporting role in mitotic cells. They also take part in the regulation of cell motility, proliferation, differentiation, and apoptosis. However, their specific functions during meiosis are largely unknown. Here, a unique role of an intermediate filament protein beaded filament structural protein 2 (BFSP2) is reported, which is predominantly expressed in lens fiber epithelial cells, as a spindle formation controller in oocyte meiosis. BFSP2 is constantly expressed during oocyte meiotic maturation, and specifically distributed on the spindle apparatus at metaphase I (MI) and metaphase II (MII) stages. Depletion of BFSP2 resulted in the meiotic arrest at MI stage due to the aberrant spindle assembly-induced spindle assembly checkpoint activation. Depletion of BFSP2 also led to incorrect kinetochore-microtubule attachments and the occurrence of aneuploidy in oocytes. Mechanistically, immunoprecipitation combined with mass spectrometry analysis identified clathrin heavy chain 1 (CLTC) as the downstream mediator of BFSP2 during meiotic spindle assembly. It is further determined that BFSP2 recruited the molecular chaperone heat shock cognate protein 70 (HSC70) to the spindle apparatus for stabilizing CLTC, and thus driving the spindle formation. In summary, these findings uncover a noncanonical function of the intermediate filament protein BFSP2 as a spindle assembly controller in oocyte meiosis.

Keywords:  BFSP2; CLTC; HSC70; intermediate filaments; oocyte meiosis; spindle assembly

DOI:  https://doi.org/10.1002/advs.202506639
Nat Commun. 2025 Jul 01. 16(1): 5755

An ex vivo uterine system captures implantation, embryogenesis, and trophoblast invasion via maternal-embryonic signaling.

Takehiro Hiraoka, Shizu Aikawa, Daisuke Mashiko, Tatsuya Nakagawa, Hiroki Shirai, Yasushi Hirota, Hiroshi Kimura, Masahito Ikawa.

Embryo implantation remains challenging to study because of its inaccessibility in situ despite its essentiality and clinical significance. Although recent studies on long-term culture of authentic and model embryos have provided significant advances in elucidating embryogenesis in vitro, they, without the uterus, cannot genuinely replicate implantation. Here, we have recapitulated bona fide implantation ex vivo at more than 90% efficiency followed by embryogenesis and trophoblast invasion using authentic mouse embryos and uterine tissue. We utilized air-liquid interface culture method with originally developed devices manufactured with polydimethylsiloxane. Notably, the system replicated the robust induction of a maternal implantation regulator COX-2 at the attachment interface, which was accompanied by trophoblastic AKT activation, suggesting a possible signaling that mediates maternal COX-2 and embryonic AKT1 that accelerates implantation. By expanding the ex vivo findings, embryonic AKT1 transduction ameliorated defective implantation of uterine origin by a COX-2 inhibitor in vivo. The system, proposing a potentially standard platform of embryogenesis, offers a concise, reproducible, and scalable screening system, suggesting significant implications for developmental biology and therapeutic strategies for recurrent implantation failure in assisted reproductive technology.

DOI: https://doi.org/10.1038/s41467-025-60610-x
Biophys J. 2025 Jul 01. pii: S0006-3495(25)00415-1. [Epub ahead of print]

Mapping single-cell rheology of ascidian embryos in the cleavage stages using AFM.

Takahiro Kotani, Tomohiro Matsuo, Megumi Yokobor, Yosuke Tsuboyama, Yuki Miyata, Yuki Fujii, Kaori Kuribayashi-Shigetomi, Takaharu Okajima.

  During early embryo development, cell division is highly organized and synchronized. Understanding the mechanical properties of embryonic cells as a material is crucial for elucidating the physical mechanism underlying embryogenesis. Previous studies on developing embryos using atomic force microscopy (AFM) revealed that single cells of ascidian embryos in the cleavage stage stiffened and softened during cell division. However, how embryonic cells, as a compliant material, exhibit viscoelastic properties during the cell cycle remains poorly characterized. In this study, we investigated the rheological properties of embryonic cells in the animal hemisphere in the cleavage stages using stress-relaxation AFM and approach-retraction force curve AFM techniques. The AFM measurements revealed that developing single cells followed a power-law rheology observed in single-cell rheology in vitro. The embryonic cells increased the modulus (stiffness) and decreased the fluidity (the power-law exponent) towards cell division. We found three rheological states in developing embryos during the cell cycle. The correlation between the cell modulus and the fluidity during the cell cycle was collapsed onto a master curve with a negative correlation, indicating that embryonic cells tightly interacting with the neighboring cells conserved the universality of rheological behavior observed in single cells in vitro.

Keywords:  atomic force microscopy; cell cycle; embryogenesis; mechanobiology; power-law rheology; single-cell mechanics

DOI:  https://doi.org/10.1016/j.bpj.2025.06.038
Histochem Cell Biol. 2025 Jun 28. 163(1): 70

A comprehensive review of histone modifications during mammalian oogenesis and early embryo development.

Nazlican Bozdemir, Tuba Kablan, Efe Biyikli, Ozgur Cinar, Fatma Uysal.

  The success of both oogenesis and early embryo development relies heavily on dynamic epigenetic regulation in which gene activity changes without affecting the underlying DNA sequence. Epigenetics works through two main mechanisms: DNA methylation and histone modifications. DNA methylation typically leads to gene silencing, while histone modifications can either activate or repress genes depending on the specific modification, histone type, and targeted amino acid residue. Histone modifications affect important DNA regulatory processes in which the histone core area as well as the N-terminal tails that extend from the core region are vulnerable to a variety of posttranslational modifications (PTMs), including methylation, citrullination (deimination), acetylation, phosphorylation, ubiquitination, SUMOylation, ribosylation, and lactylation. This review article focuses on what is known about changes in the histone modifications and how these modifications and their responsible enzymes operate throughout mammalian oocyte maturation and early embryo development, highlighting their crucial roles in these processes.

Keywords:  Early embryo development; Epigenetics; Histone modifications; Oogenesis; Preimplantation embryos

DOI:  https://doi.org/10.1007/s00418-025-02398-x
Nat Ecol Evol. 2025 Jul 01.

Cell type and cell signalling innovations underlying mammalian pregnancy.

Daniel J Stadtmauer, Silvia Basanta, Jamie D Maziarz, Alison G Cole, Gülay Dagdas, Gilbecca Rae Smith, Frank van Breukelen, Mihaela Pavličev, Günter P Wagner.

How fetal and maternal cell types have co-evolved to enable mammalian placentation poses a unique evolutionary puzzle. Here we integrate and compare single-cell transcriptomes from six species bracketing therian mammal diversity: opossum (a marsupial), Malagasy common tenrec (an afrotherian), mouse and guinea pig (rodents), and macaque and human (primates). We identify a conserved transcriptomic signature of invasive trophoblast across eutherians, probably representing a cell type family that radiated with the evolution of haemochorial placentation. In the maternal stroma, comparative analysis reveals that the endocrine decidual cell evolved from an immunomodulatory predecidual cell type retained in Tenrec and resembling early human decidua. Fetal and maternal cell signalling shows a pronounced tendency towards disambiguation-the exclusive expression of ligands by only one partner-although few ligand-receptor pairs follow an escalatory arms race dynamic. Finally, we reconstruct the uteroplacental cell-cell communication networks of extinct mammalian ancestors, identifying signalling innovations and widespread integration of fetal trophoblast and maternal decidual cells into signalling networks. Together, these results reveal a dynamic history of cell type innovation and co-evolution at the fetal-maternal interface.

DOI: https://doi.org/10.1038/s41559-025-02748-x