ENAGenomicsDana-Farber Cancer Institutehttps://www.ebi.ac.uk/ena/browser/view/PRJNA309701Mus musculusB 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. Overall design: We crossed the Bcl11a floxed strain to the interferon-inducible Mx1-Cre mouse strain (Kühn et al., 1995) to evaluate the role of Bcl11a in postnatal hematopoiesis. From this cross we obtained non-deleted (WT Bcl11afl/fl x Mx1-Cre–), heterozygously deleted (Het Bcl11afl/wt x Mx1-Cre+) and homozygously deleted (KO Bcl11afl/fl x Mx1-Cre+) animals. To induce Bcl11a gene deletion, mice were administered five injections of Polyinosinic:polycytidylic acid, p(I:C) (Figure 2A). Hematopoietic stem cells from WT, Het and KO mouse were selected for RNA extraction and hybridization on Affymetrix microarrays. Each group contains three biological replicates.xref:PubMed:27653684ENAHematopoietic Progenitor Cell, Evi9c, hematopoietic precursor cell, Evi9b, Evi9a, mKIAA1809, Hematopoietic Colony-Forming Units, BCL-11A, hemopoietic stem cell, Unit, CTIP1, Colony-Forming Units, Progenitor Cells, Stem Cells, Progenitor Cell, Phenotypes., BCL11A-S, Aging, HSC, BCL11A-L, Cell, Evi9, EVI9, blood forming stem cell, hemopoietic progenitor cell, Colony-Forming Unit, Hematopoietic Stem, hematopoietic progenitor cell, Stem Cell, Biological, Units, colony forming unit hematopoietic, HBFQTL5, Hematopoietic Colony-Forming Unit, BCL11a-M, Hematopoietic Colony-Forming, Senescence, Hematopoietic, Hematopoietic Progenitor, CFU-S, BCL11A-XL, Colony Forming Units, HSC cell, Hematopoietic Stem Cell, Ctip1, Hematopoietic Progenitor Cells, Biological Aging, 2810047E18Rik, blutbildende Stammzelle, D930021L15Rik, progenitor cell, Cells, Bcl11a, ZNF856, colony forming unit spleenMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusBcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype2025-09-242016-09-21PRJNA309701GSE772071009027653684