Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation.
| Authors | |
| Abstract | 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. |
| Year of Publication | 2017
|
| Journal | Cell Stem Cell
|
| Volume | 20
|
| Issue | 1
|
| Pages | 87-101
|
| Date Published | 2017 Jan 05
|
| ISSN | 1875-9777
|
| DOI | 10.1016/j.stem.2016.10.006
|
| PubMed ID | 27989770
|
| PubMed Central ID | PMC5218861
|
| Links | |
| Grant list | R01 MH104610 / MH / NIMH NIH HHS / United States
F31 GM115122 / GM / NIGMS NIH HHS / United States
R01 HD079546 / HD / NICHD NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
P01 GM099134 / GM / NIGMS NIH HHS / United States
R01 CA084198 / CA / NCI NIH HHS / United States
|