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Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype.

Authors :
Luc, Sidinh
Huang, Jialiang
McEldoon, Jennifer L.
Somuncular, Ece
Li, Dan
Rhodes, Claire
Mamoor, Shahan
Hou, Serena
Xu, Jian
Orkin, Stuart H.
Source :
Cell Reports; Sep2016, Vol. 16 Issue 12, p3181-3194, 14p
Publication Year :
2016

Abstract

Summary B cell CLL/lymphoma 11A (BCL11A) is a transcription factor and regulator of hemoglobin switching that has emerged as a promising therapeutic target for sickle cell disease and thalassemia. In the hematopoietic system, BCL11A is required for B lymphopoiesis, yet its role in other hematopoietic cells, especially hematopoietic stem cells (HSCs) remains elusive. The extensive expression of BCL11A in hematopoiesis implicates context-dependent roles, highlighting the importance of fully characterizing its function as part of ongoing efforts for stem cell therapy and regenerative medicine. Here, we demonstrate that BCL11A is indispensable for normal HSC function. Bcl11a deficiency results in HSC defects, typically observed in the aging hematopoietic system. We find that downregulation of cyclin-dependent kinase 6 ( Cdk6 ), and the ensuing cell-cycle delay, correlate with HSC dysfunction. Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
26391856
Volume :
16
Issue :
12
Database :
Complementary Index
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
118179951
Full Text :
https://doi.org/10.1016/j.celrep.2016.08.064