Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci.
Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci.
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DOI：
10.1016/j.stem.2011.07.007
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发表时间：
2011-09-02
期刊：
影响因子：
23.9
通讯作者：
Kim, Carla F.
中科院分区：
文献类型：
--
作者：
Zacharek, Sima J.;Fillmore, Christine M.;Lau, Allison N.;Gludish, David W.;Chou, Alan;Ho, Joshua W. K.;Zamponi, Raffaella;Gazit, Roi;Bock, Christoph;Jaeger, Natalie;Smith, Zachary D.;Kim, Tae-min;Saunders, Arven H.;Wong, Janice;Lee, Joo-Hyeon;Roach, Rebecca R.;Rossi, Derrick J.;Meissner, Alex;Gimelbrant, Alexander A.;Park, Peter J.;Kim, Carla F.
Bmi1是许多组织中干细胞自我更新所必需的，包括肺上皮干细胞、支气管肺泡干细胞（BASCs）。印迹基因，表现出只从母系或父系遗传的等位基因的表达，已知调节发育过程，但它们在成体细胞中的作用仍然是一个基本问题。许多印迹基因在Bmi1敲除小鼠中被去抑制，Cdkn1c（p57）和其他印迹基因的敲除部分挽救了Bmi1突变肺细胞的自我更新缺陷。p57和其他印记基因的表达是培养中肺细胞自我更新所必需的，并且与体内肺上皮细胞损伤的修复相关。我们的数据表明，Bmi1依赖性调节表达的等位基因在印记基因座，不同于印记本身，是需要控制肺干细胞。我们预计，印记基因的调节和功能是至关重要的自我更新在不同的成人组织特异性干细胞。
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 their role in adult cells remains a fundamental question. Many imprinted genes were de-repressed 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.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0803574105
发表时间：
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影响因子：
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作者：
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