Preventing erosion of X-chromosome inactivation in human embryonic stem cells

Marissa Cloutier, Surinder Kumar, Emily Buttigieg, Laura Keller, Brandon Lee, Aaron Williams, Sandra Mojica-Perez, Indri Erliandri, Andre Monteiro Da Rocha, Kenneth Cadigan, Gary D. Smith and Sundeep Kalantry ()
Additional contact information
Marissa Cloutier: University of Michigan Medical School
Surinder Kumar: University of Michigan Medical School
Emily Buttigieg: University of Michigan Medical School
Laura Keller: University of Michigan Medical School
Brandon Lee: University of Michigan Medical School
Aaron Williams: University of Michigan Medical School
Sandra Mojica-Perez: University of Michigan Medical School
Indri Erliandri: University of Michigan Medical School
Andre Monteiro Da Rocha: University of Michigan Medical School
Kenneth Cadigan: Cellular, and Developmental Biology, University of Michigan Medical School
Gary D. Smith: University of Michigan Medical School
Sundeep Kalantry: University of Michigan Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract X-chromosome inactivation is a paradigm of epigenetic transcriptional regulation. Female human embryonic stem cells (hESCs) often undergo erosion of X-inactivation upon prolonged culture. Here, we investigate the sources of X-inactivation instability by deriving new primed pluripotent hESC lines. We find that culture media composition dramatically influenced the expression of XIST lncRNA, a key regulator of X-inactivation. hESCs cultured in a defined xenofree medium stably maintained XIST RNA expression and coating, whereas hESCs cultured in the widely used mTeSR1 medium lost XIST RNA expression. We pinpointed lithium chloride in mTeSR1 as a cause of XIST RNA loss. The addition of lithium chloride or inhibitors of GSK-3 proteins that are targeted by lithium to the defined hESC culture medium impeded XIST RNA expression. GSK-3 inhibition in differentiating female mouse embryonic stem cells and epiblast stem cells also resulted in a loss of XIST RNA expression. Together, these data may reconcile observed variations in X-inactivation in hESCs and inform the faithful culture of pluripotent stem cells.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-30259-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30259-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-30259-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().