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

Citation:

Zacharek SJ, Fillmore CM, Lau AN, Gludish DW, Chou A, Ho JWK, Zamponi R, Gazit R, Bock C, Jäger N, Smith ZD, Kim T-M, Saunders AH, Wong J, Lee J-H, Roach RR, Rossi DJ, Meissner A, Gimelbrant AA, Park PJ, Kim CF. Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci. Cell Stem Cell 2011;9(3):272-81. Copy at http://www.tinyurl.com/yydkkll9

Date Published:

2011 Sep 2

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.

Last updated on 10/21/2015