PLX296111

GSE87237: Human nave pluripotent stem cells exhibit X chromosome dampening and X-inactivation (single cell RNA-Seq)

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Nave 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 nave 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 nave 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 nave state reset Xi abnormalities of primed hESCs, providing cells better suited for downstream applications. However, nave 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. SOURCE: Shan Sabri (ShanSabri@mednet.ucla.edu) - University of California, Los Angeles