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

Sidinh Luc, Jialiang Huang, Jennifer L. McEldoon, Ece Somuncular, Dan Li, Claire Rhodes, Shahan Mamoor, Serena Hou, Jian Xu, Stuart H. Orkin

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3181-3194
Number of pages14
JournalCell Reports
Volume16
Issue number12
DOIs
StatePublished - Sep 20 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Luc, S., Huang, J., McEldoon, J. L., Somuncular, E., Li, D., Rhodes, C., Mamoor, S., Hou, S., Xu, J., & Orkin, S. H. (2016). Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. Cell Reports, 16(12), 3181-3194. https://doi.org/10.1016/j.celrep.2016.08.064