title: Histone deacetylase inhibition elicits an evolutionarily conserved self-renewal program in embryonic stem cells.
abstract: Recent evidence indicates that mouse and human embryonic stem cells (ESCs) are fixed at different developmental stages, with the former positioned earlier. We show that a narrow concentration of the naturally occurring short-chain fatty acid, sodium butyrate, supports the extensive self-renewal of mouse and human ESCs, while promoting their convergence toward an intermediate stem cell state. In response to butyrate, human ESCs regress to an earlier developmental stage characterized by a gene expression profile resembling that of mouse ESCs, preventing precocious Xist expression while retaining the ability to form complex teratomas in vivo. Other histone deacetylase inhibitors (HDACi) also support human ESC self-renewal. Our results indicate that HDACi can promote ESC self-renewal across species, and demonstrate that ESCs can toggle between alternative states in response to environmental factors.
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA. cware@u.washington.edu
authors.forename: Carol B
authors.initials: CB
authors.lastname: Ware
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.forename: Brigham H
authors.initials: BH
authors.lastname: Mecham
authors.forename: Lanlan
authors.initials: L
authors.lastname: Shen
authors.forename: Angelique M
authors.initials: AM
authors.lastname: Nelson
authors.forename: Merav
authors.initials: M
authors.lastname: Bar
authors.forename: Deepak A
authors.initials: DA
authors.lastname: Lamba
authors.forename: Derek S
authors.initials: DS
authors.lastname: Dauphin
authors.forename: Brian
authors.initials: B
authors.lastname: Buckingham
authors.forename: Bardia
authors.initials: B
authors.lastname: Askari
authors.forename: Raymond
authors.initials: R
authors.lastname: Lim
authors.forename: Muneesh
authors.initials: M
authors.lastname: Tewari
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Gartler
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Issa
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Duan
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Blau