title: Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci.
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.
authors: Stem Cell Program, Children's Hospital Boston, Boston, MA 02115 USA.
authors: Sima J
authors: SJ
authors: Zacharek
authors: Christine M
authors: CM
authors: Fillmore
authors: Allison N
authors: AN
authors: Lau
authors: David W
authors: DW
authors: Gludish
authors: Alan
authors: A
authors: Chou
authors: Joshua W K
authors: JW
authors: Ho
authors: Raffaella
authors: R
authors: Zamponi
authors: Roi
authors: R
authors: Gazit
authors: Christoph
authors: C
authors: Bock
authors: Natalie
authors: N
authors: Jäger
authors: Zachary D
authors: ZD
authors: Smith
authors: Tae-min
authors: TM
authors: Kim
authors: Arven H
authors: AH
authors: Saunders
authors: Janice
authors: J
authors: Wong
authors: Joo-Hyeon
authors: JH
authors: Lee
authors: Rebecca R
authors: RR
authors: Roach
authors: Derrick J
authors: DJ
authors: Rossi
authors: Alex
authors: A
authors: Meissner
authors: Alexander A
authors: AA
authors: Gimelbrant
authors: Peter J
authors: PJ
authors: Park
authors: Carla F
authors: CF
authors: Kim
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D019942:Genes, p16 / Q000502:physiology; D056426:Genetic Loci; D018392:Genomic Imprinting / Q000235:genetics; D008168:Lung / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C489421:Bmi1 protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D044786:S-Phase Kinase-Associated Proteins; D063150:Polycomb Repressive Complex 1