Document Detail

Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin.
MedLine Citation:
PMID:  22058289     Owner:  NLM     Status:  MEDLINE    
Human embryonic stem cells (hESCs) are pluripotent cell types derived from the inner cell mass of human blastocysts. Recent data indicate that the majority of established female XX hESC lines have undergone X chromosome inactivation (XCI) prior to differentiation, and XCI of hESCs can be either XIST-dependent (class II) or XIST-independent (class III). XCI of female hESCs precludes the use of XX hESCs as a cell-based model for examining mechanisms of XCI, and will be a challenge for studying X-linked diseases unless strategies are developed to reactivate the inactive X. In order to recover nuclei with two active X chromosomes (class I), we developed a reprogramming strategy by supplementing hESC media with the small molecules sodium butyrate and 3-deazaneplanocin A (DZNep). Our data demonstrate that successful reprogramming can occur from the XIST-dependent class II nuclear state but not class III nuclear state. To determine whether these small molecules prevent XCI, we derived six new hESC lines under normoxic conditions (UCLA1-UCLA6). We show that class I nuclei are present within the first 20 passages of hESC derivation prior to cryopreservation, and that supplementation with either sodium butyrate or DZNep preserve class I nuclei in the self-renewing state. Together, our data demonstrate that self-renewal and survival of class I nuclei are compatible with normoxic hESC derivation, and that chemical supplementation after derivation provides a strategy to prevent epigenetic progression and retain nuclei with two active X chromosomes in the self-renewing state.
Silvia V Diaz Perez; Rachel Kim; Ziwei Li; Victor E Marquez; Sanjeet Patel; Kathrin Plath; Amander T Clark
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-11-04
Journal Detail:
Title:  Human molecular genetics     Volume:  21     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-24     Completed Date:  2012-07-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  751-64     Citation Subset:  IM    
Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA, USA.
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MeSH Terms
Adenosine / analogs & derivatives,  pharmacology
Butyrates / pharmacology
Cell Culture Techniques
Cell Differentiation
Cell Line
Chromatin / chemistry,  drug effects*,  metabolism
Chromosomes, Human, X / genetics
Embryonic Stem Cells / cytology*,  drug effects,  metabolism*
Epigenesis, Genetic / drug effects*
Nuclear Reprogramming / drug effects,  genetics
RNA, Long Untranslated
RNA, Untranslated / genetics
Grant Support
Reg. No./Substance:
0/Butyrates; 0/Chromatin; 0/RNA, Long Untranslated; 0/RNA, Untranslated; 0/XIST non-coding RNA; 102052-95-9/3-deazaneplanocin; 58-61-7/Adenosine

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