Lung stem cell self-renewal relies on BMI1-dependent control of expression at imprinted loci.
نویسندگان
چکیده
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.
منابع مشابه
Bmi1 is critical for lung tumorigenesis and bronchioalveolar stem cell expansion.
Understanding the pathways that control epithelial carcinogenesis is vital to the development of effective treatments. The Polycomb group family member Bmi1 is overexpressed in numerous epithelial tumors, but its role in their development has not been established. We now show a key role for Bmi1 in lung adenocarcinoma. Whereas lung development occurs normally in Bmi1-deficient mice, loss of Bmi...
متن کاملCathepsin B and uPAR regulate self-renewal of glioma-initiating cells through GLI-regulated Sox2 and Bmi1 expression.
Cancer-initiating cells comprise a heterogeneous population of undifferentiated cells with the capacity for self-renewal and high proliferative potential. We investigated the role of uPAR and cathepsin B in the maintenance of stem cell nature in glioma-initiating cells (GICs). Simultaneous knockdown of uPAR and cathepsin B significantly reduced the expression of CD133, Nestin, Sox2 and Bmi1 at ...
متن کاملPolycomb Group Protein Bmi1 Is Required for Growth of RAF Driven Non-Small-Cell Lung Cancer
BACKGROUND We have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1. PRINCIPAL FINDINGS In order to evaluate Bmi1 function in NSCLC two founder lines that differ in incidence and latency of tumor formation were compared. Ablation of Bmi1 ...
متن کاملLong-term maintenance of human hematopoietic stem/progenitor cells by expression of BMI1.
The polycomb group (PcG) gene BMI1 has been identified as one of the key epigenetic regulators of cell fates during different stages of development in multiple murine tissues. In a clinically relevant model, we demonstrate that enforced expression of BMI1 in cord blood CD34(+) cells results in long-term maintenance and self-renewal of human hematopoietic stem and progenitor cells. Long-term cul...
متن کاملshRNA targeting Bmi1 impedes the self-renewal of cisplatin-enriched stem-like cells in human A549 cells.
It has been hypothesized that cancer stem-like cells are responsible for tumor recurrence following chemotherapy. Evidence on the mechanisms through which drug-resistant stem-like cells recapitulate the tumor mass has not been definitively reported. Based on this information, we investigated the enrichment ability of a population of stem-like cell...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cell stem cell
دوره 9 3 شماره
صفحات -
تاریخ انتشار 2011