Esrrb is a cell-cycle-dependent associated factor balancing pluripotency and XEN differentiation.

ChIP-seq and single-cell RNA-seq (scRNA-seq) Esrrb transcription factor Exit from pluripotency cell cycle cellular differentiation and lineage specification embryonic stem cells epiblast stem cells (EpiSC) extraembryonic endoderm stem cells(XEN)

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
14 06 2022
Historique:
received: 08 02 2022
revised: 25 04 2022
accepted: 25 04 2022
pubmed: 21 5 2022
medline: 18 6 2022
entrez: 20 5 2022
Statut: ppublish

Résumé

Cell cycle and differentiation decisions are linked; however, the underlying principles that drive these decisions are unclear. Here, we combined cell-cycle reporter system and single-cell RNA sequencing (scRNA-seq) profiling to study the transcriptomes of embryonic stem cells (ESCs) in the context of cell-cycle states and differentiation. By applying retinoic acid, to G1 and G2/M ESCs, we show that, while both populations can differentiate toward epiblast stem cells (EpiSCs), only G2/M ESCs could differentiate into extraembryonic endoderm cells. We identified Esrrb, a pluripotency factor that is upregulated during G2/M, as a driver of extraembryonic endoderm stem cell (XEN) differentiation. Furthermore, enhancer chromatin states based on wild-type (WT) and ESRRB knockout (KO) ESCs show association of ESRRB with XEN poised enhancers. G1 cells overexpressing Esrrb allow ESCs to produce XENs, while ESRRB-KO ESCs lost their potential to differentiate into XEN. Overall, this study reveals a vital link between Esrrb and cell-cycle states during the exit from pluripotency.

Identifiants

pubmed: 35594859
pii: S2213-6711(22)00205-3
doi: 10.1016/j.stemcr.2022.04.016
pmc: PMC9214067
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1334-1350

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Sapir Herchcovici Levy (S)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Sharon Feldman Cohen (S)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Lee Arnon (L)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Shlomtzion Lahav (S)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Muhammad Awawdy (M)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Adi Alajem (A)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Danny Bavli (D)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Xue Sun (X)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.

Yosef Buganim (Y)

Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel.

Oren Ram (O)

Department of Biological Chemistry, Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. Electronic address: oren.ram@mail.huji.ac.il.

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