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Human naive pluripotent stem cells exhibit X chromosome dampening and X-inactivation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE87239 | GEO | 2016/10/21

SECONDARY ACCESSION(S): PRJNA343940

REPOSITORIES: GEO

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Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.

Project description:Naive human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X chromosome state has remained unresolved. Here, we show that the inactive X chromosome (Xi) of primed hESCs was reactivated in naive culture conditions. Like cells of the blastocyst, the resulting naive cells contained two active X chromosomes with XIST expression and chromosome-wide transcriptional dampening and initiated XIST-mediated X inactivation upon differentiation. Both establishment of and exit from the naive state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X chromosome dosage compensation processes in early human development: X dampening and X inactivation. However, remaining differences between naive hESCs and embryonic cells related to mono-allelic XIST expression and non-random X inactivation highlight the need for further culture improvement. As the naive state resets Xi abnormalities seen in primed hESCs, it may provide cells better suited for downstream applications.

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Human naive pluripotent stem cells exhibit X chromosome dampening and X-inactivation

Project description:Human naive pluripotent stem cells exhibit X chromosome dampening and X-inactivation

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Human naïve pluripotent stem cells exhibit X chromosome dampening and X-inactivation (RRBS)

Project description:Naïve human embryonic stem cells (hESCs) can be derived from primed hESCs or directly from blastocysts, but their X-chromosome state has remained unresolved. We found that the inactive X-chromosome (Xi) of primed hESCs was reactivated in naïve culture conditions. Similar to cells of the blastocyst, resulting naive cells exhibited two active X-chromosomes with XIST expression and chromosome-wide transcriptional dampening, and initiated XIST-mediated X-inactivation upon differentiation. Both establishment and exit from the naïve state (differentiation) happened via an XIST-negative XaXa intermediate. Together, these findings identify a cell culture system for functionally exploring the two X-chromosome dosage compensation processes in early human development: X-dampening and X-inactivation. Furthermore, the naïve state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, naïve hESCs displayed differences to the embryo because XIST expression was predominantly mono-allelic instead of bi-allelic, and X-inactivation was non-random, indicating the need for further culture improvement.

2016-10-21 | GSE87235 | GEO

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Single-Cell Analysis Reveals Partial Reactivation of X Chromosome instead of Chromosome-wide Dampening in Naive Human Pluripotent Stem Cells.

Project description:Recently, a unique form of X chromosome dosage compensation has been demonstrated in human preimplantation embryos, which happens through the dampening of X-linked gene expression from both X chromosomes. Subsequently, X chromosome dampening has also been demonstrated in female human pluripotent stem cells (hPSCs) during the transition from primed to naive state. However, the existence of dampened X chromosomes in both embryos and hPSCs remains controversial. Specifically, in preimplantation embryos it has been shown that there is inactivation of X chromosome instead of dampening. Here, we performed allelic analysis of X-linked genes at the single-cell level in hPSCs and found that there is partial reactivation of the inactive X chromosome instead of chromosome-wide dampening upon conversion from primed to naive state. In addition, our analysis suggests that the reduced X-linked gene expression in naive hPSCs might be the consequence of erasure of active X chromosome upregulation.

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Molecular Criteria for Defining the Naive Human Pluripotent State

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Spen regulates X chromosome inactivation

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