Esrrb conveys naive pluripotent cells through the formative transcriptional program
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ABSTRACT:
PROVIDER: PRJNA763240 | ENA |
REPOSITORIES: ENA
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Project description:We report the application of genome-wide RNA-sequencing analysis for pluripotent wild-type or Esrrb KO mouse ES cells, maintained in 2iL or differentiated for 24, 48 or 72 hours. We find an anticipated progression of Esrrb KO cells as compared to wild-type cells and a massive downregulation of formative genes in multiple Esrrb KO clones, confirming the role of Esrrb as an inducer of the formative program. Such Esrrb KO cells also show upregulation of committed genes and activation of the Mesendoderm program.
2023-01-25 | GSE184133 | GEO
Project description:We report the application of sequencing technology for profiling of genome-wide ESRRB binding in mouse ES cells. We generated genome-wide chromatin-state maps of mouse embryonic stem cells maintained in pluripotent state (2iL) and differentiated for 48 and 96 hours (48 and 96). We find that the large majority of ESRRB binding occurs in 2iL and at 48 hours and that several formative genes promoters are bound by ESRRB in 2iL and at 48h. Moreover ESRRB peaks on naïve genes (e.g. Tfcp2l1, Nanog) decrease as soon as cells start differentiating while peaks on formative genes are present in 2iL and the signal is maintained (or increased) at 48 hours, further endorsing the concept of Esrrb as a direct activator of the formative gene program during the Reversible phase.
2023-01-25 | GSE184131 | GEO
Project description:We report the application of genome-wide RNA-sequencing analysis for pluripotent mouse ES cells transfected with DOX-inducible Esrrb and maintained in 2iL, or differentiated for 96 hours with or without Doxycycline. We find that Esrrb expression is sufficient to confer reversibility and activates both naive and formative genes.
2023-01-25 | GSE184132 | GEO
Project description:During embryonic development, naive pluripotent epiblast cells transit to a formative state. The formative epiblast cells form a polarized epithelium, exhibit distinct transcriptional and epigenetic profiles and acquire competence to differentiate into all somatic and germline lineages. However, we have limited understanding of how the transition to a formative state is molecularly controlled. Here we used murine embryonic stem cell models to show that ESRRB is both required and sufficient to activate formative genes. Genetic inactivation of Esrrb leads to illegitimate expression of mesendoderm and extra-embryonic markers, impaired formative expression and failure to self-organize in 3D. Functionally, this results in impaired ability to generate formative stem cells and primordial germ cells in the absence of Esrrb. Computational modelling and genomic analyses revealed that ESRRB occupies key formative genes in naive cells and throughout the formative state. In so doing, ESRRB kickstarts the formative transition, leading to timely and unbiased capacity for multi-lineage differentiation.
| S-EPMC7614557 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-01-25 | GSE184137 | GEO
Project description:We report the application of genome-wide RNA-sequencing analysis for Esrrb WT and conditional Esrrb KO mES cells after differentation for 48 hours. Global transcriptome profiling revealed impaired induction of formative genes in conditional KO cells compared to WT cells.
2023-01-25 | GSE217802 | GEO
Project description:We report the application of genome-wide RNA-sequencing analysis for Esrrb WT and Esrrb KO mES cells after differentiation towards Formative Stem cells (FS cells). We find that expression of some formative genes was reduced in Esrrb KO cells compared to WT, and that lineage markers were significantly upregulated in Esrrb KO cells. This indicates that transition toward the formative state is impaired in Esrrb KO cells.
2023-01-25 | GSE208703 | GEO
Project description:Early during preimplantation development and in heterogeneous mouse embryonic stem cells (mESC) culture, pluripotent cells are specified towards either the primed epiblast or the primitive endoderm (PE) lineage. Canonical Wnt signaling is crucial for safeguarding naive pluripotency and embryo implantation, yet the role and relevance of canonical Wnt inhibition during early mammalian development remains unknown. Here, we demonstrate that transcriptional repression exerted by Wnt/TCF7L1 promotes PE differentiation of mESCs and in preimplantation inner cell mass. Time-series RNA sequencing and promoter occupancy data reveal that TCF7L1 binds and represses genes encoding essential naive pluripotency factors and indispensable regulators of the formative pluripotency program, including Otx2 and Lef1. Consequently, TCF7L1 promotes pluripotency exit and suppresses epiblast lineage formation, thereby driving cells into PE specification. Conversely, TCF7L1 is required for PE specification as deletion of Tcf7l1 abrogates PE differentiation without restraining epiblast priming. Taken together, our study underscores the importance of transcriptional Wnt inhibition in regulating lineage specification in ESCs and preimplantation embryo development as well as identifies TCF7L1 as key regulator of this process.
2023-02-08 | GSE171204 | GEO
Project description:Two phases of pluripotency, naïve and primed, have been captured in vitro and studied in details1. A third formative phase was recently proposed to exist between naïve and primed phases2. Formative pluripotency entails permissiveness for direct primordial germ cell (PGC) induction and competence for blastocyst chimeras, and is characterized by transcriptional and epigenetic features intermediate of naïve and primed pluripotency. To date, however, stable pluripotent stem cells (PSCs) harboring formative features haven’t been derived from early mammalian embryos. Here we develop a method which enabled the derivation and culture of stable formative-like embryonic stem cells (ESCs) from mouse blastocysts. Formative-like mouse ESCs share molecular features characteristic of early post-implantation epiblasts and are competent for PGC-like cell induction and blastocyst chimera formation. The same culture also supported the derivation of ESCs and transgene-free induced pluripotent stem cells (iPSCs) from horse blastocysts and fibroblasts, respectively. Horse ESCs/iPSCs transcriptionally resembled mouse formative cells, and could also be directly induced into PGC-like cells. Formative-like horse iPSCs could efficiently chimerize horse, mouse, goat, sheep and pig embryos. Stable formative-like PSCs will be invaluable for studying mammalian pluripotency, and our method may be broadly applicable for the derivation of PGC and chimera competent PSCs from other mammalian species.
2020-11-27 | GSE135990 | GEO
Project description:Two phases of pluripotency, naïve and primed, have been captured in vitro and studied in details1. A third formative phase was recently proposed to exist between naïve and primed phases2. Formative pluripotency entails permissiveness for direct primordial germ cell (PGC) induction and competence for blastocyst chimeras, and is characterized by transcriptional and epigenetic features intermediate of naïve and primed pluripotency. To date, however, stable pluripotent stem cells (PSCs) harboring formative features haven’t been derived from early mammalian embryos. Here we develop a method which enabled the derivation and culture of stable formative-like embryonic stem cells (ESCs) from mouse blastocysts. Formative-like mouse ESCs share molecular features characteristic of early post-implantation epiblasts and are competent for PGC-like cell induction and blastocyst chimera formation. The same culture also supported the derivation of ESCs and transgene-free induced pluripotent stem cells (iPSCs) from horse blastocysts and fibroblasts, respectively. Horse ESCs/iPSCs transcriptionally resembled mouse formative cells, and could also be directly induced into PGC-like cells. Formative-like horse iPSCs could efficiently chimerize horse, mouse, goat, sheep and pig embryos. Stable formative-like PSCs will be invaluable for studying mammalian pluripotency, and our method may be broadly applicable for the derivation of PGC and chimera competent PSCs from other mammalian species.
2020-11-27 | GSE135989 | GEO