Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci

Sima J. Zacharek, Christine M. Fillmore, Allison N. Lau, David W. Gludish, Alan Chou, Joshua W.K. Ho, Raffaella Zamponi, Roi Gazit, Christoph Bock, Natalie Jäger, Zachary D. Smith, Tae Min Kim, Arven H. Saunders, Janice Wong, Joo Hyeon Lee, Rebecca R. Roach, Derrick J. Rossi, Alex Meissner, Alexander A. Gimelbrant, Peter J. ParkCarla F. Kim

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

BMI1 is required for the self-renewal of stem cells in many tissues including the lung epithelial stem cells, Bronchioalveolar Stem Cells (BASCs). Imprinted genes, which exhibit expression from only the maternally or paternally inherited allele, are known to regulate developmental processes, but what their role is in adult cells remains a fundamental question. Many imprinted genes were derepressed in Bmi1 knockout mice, and knockdown of Cdkn1c (p57) and other imprinted genes partially rescued the self-renewal defect of Bmi1 mutant lung cells. Expression of p57 and other imprinted genes was required for lung cell self-renewal in culture and correlated with repair of lung epithelial cell injury in vivo. Our data suggest that BMI1-dependent regulation of expressed alleles at imprinted loci, distinct from imprinting per se, is required for control of lung stem cells. We anticipate that the regulation and function of imprinted genes is crucial for self-renewal in diverse adult tissue-specific stem cells.

Original languageEnglish
Pages (from-to)272-281
Number of pages10
JournalCell Stem Cell
Volume9
Issue number3
DOIs
StatePublished - 2 Sep 2011
Externally publishedYes

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