Epigenetic control of cell identities from epiblast to gastrulation DOI Creative Commons
Katrin M. Schüle, Simone Probst

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Epigenetic modifications of chromatin are essential for the establishment cell identities during embryogenesis. Between embryonic days 3.5–7.5 murine development, major lineage decisions made that discriminate extraembryonic and tissues, primary germ layers formed, thereby laying down basic body plan. In this review, we cover contribution dynamic by DNA methylation, changes accessibility, histone modifications, in combination with transcription factors control gene expression programs different types. We highlight differences regulation enhancer promoter marks discuss their requirement specification. Importantly, many cases, lineage‐specific targeting epigenetic modifiers is carried out pioneer or master factors, sum mediate landscape cell‐type‐specific thus, identities.

Язык: Английский

High resolution multi-scale profiling of embryonic germ cell-like cells derivation reveals pluripotent state transitions in humans DOI Creative Commons
S. Stucchi, Lessly P. Sepulveda-Rincon, Camille Dion

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract Primordial germ cells (PGCs) are the embryonic precursors of gametes. In mice and rats, PGCs can readily acquire pluripotency in vitro by forming (EGCs). To date, a comparable system has not been established humans, despite fact that human (hPGCs) undergo pluripotent conversion context cell tumorigenesis. Here we report hPGC-like (hPGCLCs) to germ-like (hEGCLCs) upon exposure same inductive signals previously used derive mouse EGCs. This defined, feeder-free culture allows efficient derivation EGCLCs which be expanded maintained standard stem medium. hEGCLCs transcriptionally similar (hPSCs) differentiate into all three layers, as well giving rise PGCLCs once more - demonstrating interconvertibility states. is also evident at epigenetic level, initial DNA demethylation occurs hPGCLCs largely reversed hEGCLCs, restoring methylation level observed hPSCs. new model captures transition from state identity back again, therefore represents highly tractable study transitions, including those occur during Graphical abstract brief We first fully defined efficiently convert (PSC) state. tracked transitions multi-omic analysis provided high-resolution map transcriptional epigenomic entry exit germline. Highlights Efficient hEGCLC conditions Single-cell transcriptomic profiling hPSC back. Longitudinal highlights overall reversibility states Multi-omic gene regulatory network identifies key regulators

Язык: Английский

Процитировано

0
Pervasive and programmed nucleosome distortion patterns on single mammalian chromatin fibers DOI Creative Commons
Marty G. Yang, Hannah J. Richter, Simai Wang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

We present a genome-scale method to map the single-molecule co-occupancy of structurally distinct nucleosomes, subnucleosomes, and other protein-DNA interactions via long-read high-resolution adenine methyltransferase footprinting. I teratively D efined L engths Inaccessibility (IDLI) classifies nucleosomes on basis shared patterns intranucleosomal accessibility, into: i.) minimally-accessible chromatosomes; ii.) octasomes with stereotyped DNA accessibility from superhelical locations (SHLs) ±1 through ±7; iii.) highly-accessible unwrapped nucleosomes; iv.) subnucleosomal species, such as hexasomes, tetrasomes, short protections. Applying IDLI mouse embryonic stem cell (mESC) chromatin, we discover widespread nucleosomal distortion individual mammalian chromatin fibers, >85% surveyed displaying degrees intranucleosomally accessible DNA. observe epigenomic-domain-specific distorted nucleosome positioning, including at enhancers, promoters, satellite repeat sequences. Nucleosome is programmed by presence bound transcription factors (TFs) cognate motifs; occupied TF binding sites are differentially decorated compared unbound sites, degradation experiments establish direct roles for TFs in structuring binding-site proximal nucleosomes. Finally, apply context primary hepatocytes, observing evidence pervasive vivo. Further genetic reveal role hepatocyte master regulator FOXA2 directly impacting hepatocyte-specific regulatory elements vivo . Our work suggests extreme-but regulated-plasticity level. Further, our study offers an essential new framework model factor binding, remodeling, cell-type specific gene regulation across biological contexts.

Язык: Английский

Процитировано

0
Reconstruction of gene regulatory networks from single cell transcriptomic data DOI Creative Commons
Mikhail A. Rybakov,

N. A. Omelyanchuk,

Elena V. Zemlyanskaya

и другие.

Vavilov Journal of Genetics and Breeding, Год журнала: 2025, Номер 28(8), С. 974 - 981

Опубликована: Янв. 26, 2025

Gene regulatory networks (GRNs) – interpretable graph models of gene expression regulation are a pivotal tool for understanding and investigating the mechanisms utilized by cells during development in response to various internal external stimuli. Historically, first approach GRN reconstruction was based on analysis published data (including those summarized databases). Currently, primary inference is omics (mainly transcriptomic) data; number mathematical methods have been adapted that. Obtaining individual has made it possible conduct large-scale molecular genetic studies with an extremely high resolution. In particular, become reconstruct GRNs cell types states. However, technical biological features single-cell require specific approaches inference. This review describes programs that used from RNA sequencing (scRNA-seq) data. We consider advantages using scRNA-seq compared bulk RNA-seq, as well challenges pay attention state-of-the-art transcriptomes recruiting other data, primarily transcription factor binding sites open chromatin profiles (scATAC-seq), order increase accuracy. The also considers applicability reconstructed recover characterize processes. Future perspectives this area discussed.

Язык: Английский

Процитировано

0
Transcription factors associated with regulation of transcriptome in human thigh and calf muscles at baseline and after six days of disuse DOI
Anna A. Borzykh, Pavel A. Makhnovskii, Ivan I. Ponomarev

и другие.

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Год журнала: 2025, Номер unknown, С. 195086 - 195086

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Epigenetic control of cell identities from epiblast to gastrulation DOI Creative Commons
Katrin M. Schüle, Simone Probst

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Epigenetic modifications of chromatin are essential for the establishment cell identities during embryogenesis. Between embryonic days 3.5–7.5 murine development, major lineage decisions made that discriminate extraembryonic and tissues, primary germ layers formed, thereby laying down basic body plan. In this review, we cover contribution dynamic by DNA methylation, changes accessibility, histone modifications, in combination with transcription factors control gene expression programs different types. We highlight differences regulation enhancer promoter marks discuss their requirement specification. Importantly, many cases, lineage‐specific targeting epigenetic modifiers is carried out pioneer or master factors, sum mediate landscape cell‐type‐specific thus, identities.

Язык: Английский

Процитировано

0