Transcriptome of primed and naïve-like state sheep embryonic stem cells
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ABSTRACT:
ORGANISM(S): Ovis aries
PROVIDER: GSE311245 | GEO | 2026/06/01
REPOSITORIES: GEO
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Project description:Mammalian pluripotent stem cells are thought to exist in two states: naïve and primed states. Generally, unlike those in rodents, pluripotent stem cells in primates including humans are regarded as being in the primed pluripotent state. Recently, several groups reported the existence of naïve pluripotent stem cells in humans. In this study, we report the conversion of primed state embryonic stem cells from common marmoset, a New World monkey, to the naïve state by using transgenes. The cells showed typical naïve state features including dome-like colony morphology, growth factor requirement, gene expression profile, X chromosome activation state, and energy metabolic status. Moreover, interspecies chimeric embryo formation ability with mouse embryos was increased in the naïve state. This technique can be applied in basic medical research using non-human primates such as preclinical use of naïve pluripotent stem cells and generating genetically modified primates.
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Project description:Expression profiling of Naïve and Primed hESCs using Illumina HT-12 v.4 expression BeadChip We report that over-expression of the transcription factor YAP in male and female human ESCs and iPSCs promotes the generation of naïve PSCs. YAP-induced naïve PSCs have a naïve-specific dome-like colony morphology, rapid clonal growth rate for more than 70 passages, normal karyotype, expression of pluripotency markers and ability to form teratomas. Lysophosphatidic acid (LPA) can substitute for YAP to generated transgene-free human naïve PSCs. We performed microarray analyses on hESCs and hIPSCs in primed and naïve ESC media and show that YAP overexpressing cells in naïve media (Ying et al 2008, Ludwig et al 2006, Theunnissen 2014) display a distinct naïve-like transcriptional profile and other hallmarks of the naïve state. These results uncover an unexpected role for YAP in the transition to the human naïve state, and provide a platform in which to further dissect this transition and probe early human embryology.
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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.
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Project description:Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine and the primary source for many novel cellular therapies. The development of naïve culture conditions has led to the expectation that these naïve hPSCs could overcome some of the limitations found in conventional (primed) hPSCs culture conditions, including recurrent epigenetic anomalies. Recent work has shown that transition to the primed state (or capacitation) is necessary for naïve hPSCs to acquire multi-lineage differentiation competence. This pluripotent state transition may recapitulate essential features of human peri-implantation development. Here we studied epigenetic changes during the transition between naïve and primed pluripotency, examining global genomic redistribution of histone modifications, chromatin accessibility, and DNA methylation, and correlating these with gene expression. We identify CpG islands, enhancers, and retrotransposons as hotspots of epigenetic dynamics between pluripotency states. Our results further reveal that hPSC resetting and subsequent capacitation rescue X chromosome-linked epigenetic erosion and reduce the ectoderm-biased gene expression of conventional primed hPSCs.
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Project description:Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine and the primary source for many novel cellular therapies. The development of naïve culture conditions has led to the expectation that these naïve hPSCs could overcome some of the limitations found in conventional (primed) hPSCs culture conditions, including recurrent epigenetic anomalies. Recent work has shown that transition to the primed state (or capacitation) is necessary for naïve hPSCs to acquire multi-lineage differentiation competence. This pluripotent state transition may recapitulate essential features of human peri-implantation development. Here we studied epigenetic changes during the transition between naïve and primed pluripotency, examining global genomic redistribution of histone modifications, chromatin accessibility, and DNA methylation, and correlating these with gene expression. We identify CpG islands, enhancers, and retrotransposons as hotspots of epigenetic dynamics between pluripotency states. Our results further reveal that hPSC resetting and subsequent capacitation rescue X chromosome-linked epigenetic erosion and reduce the ectoderm-biased gene expression of conventional primed hPSCs.
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Project description:Human pluripotent stem cells (hPSCs) are of fundamental relevance in regenerative medicine and the primary source for many novel cellular therapies. The development of naïve culture conditions has led to the expectation that these naïve hPSCs could overcome some of the limitations found in conventional (primed) hPSCs culture conditions, including recurrent epigenetic anomalies. Recent work has shown that transition to the primed state (or capacitation) is necessary for naïve hPSCs to acquire multi-lineage differentiation competence. This pluripotent state transition may recapitulate essential features of human peri-implantation development. Here we studied epigenetic changes during the transition between naïve and primed pluripotency, examining global genomic redistribution of histone modifications, chromatin accessibility, and DNA methylation, and correlating these with gene expression. We identify CpG islands, enhancers, and retrotransposons as hotspots of epigenetic dynamics between pluripotency states. Our results further reveal that hPSC resetting and subsequent capacitation rescue X chromosome-linked epigenetic erosion and reduce the ectoderm-biased gene expression of conventional primed hPSCs.
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