TY - JOUR
T1 - Esrrb is a cell-cycle-dependent associated factor balancing pluripotency and XEN differentiation
AU - Herchcovici Levy, Sapir
AU - Feldman Cohen, Sharon
AU - Arnon, Lee
AU - Lahav, Shlomtzion
AU - Awawdy, Muhammad
AU - Alajem, Adi
AU - Bavli, Danny
AU - Sun, Xue
AU - Buganim, Yosef
AU - Ram, Oren
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/6/14
Y1 - 2022/6/14
N2 - 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.
AB - 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.
KW - ChIP-seq and single-cell RNA-seq (scRNA-seq)
KW - Esrrb transcription factor
KW - Exit from pluripotency
KW - cell cycle
KW - cellular differentiation and lineage specification
KW - embryonic stem cells
KW - epiblast stem cells (EpiSC)
KW - extraembryonic endoderm stem cells(XEN)
UR - http://www.scopus.com/inward/record.url?scp=85132395463&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2022.04.016
DO - 10.1016/j.stemcr.2022.04.016
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C2 - 35594859
AN - SCOPUS:85132395463
SN - 2213-6711
VL - 17
SP - 1334
EP - 1350
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 6
ER -