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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: Not available

| S-EPMC5218861 | biostudies-literature

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