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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 20, 2016 |
| Title |
Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| 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.
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| 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.
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| Contributor(s) |
Luc S, Huang J |
| Citation(s) |
27653684 |
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| Submission date |
Jan 25, 2016 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Jialiang Huang |
| E-mail(s) |
jhuang@xmu.edu.cn
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| Organization name |
Dana-Farber Cancer Institute
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| Street address |
450 Brookline Avenue
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| GSM2046008 |
HSC, Bcl11a heterozygously deleted, biological rep1 |
| GSM2046009 |
HSC, Bcl11a heterozygously deleted, biological rep2 |
| GSM2046010 |
HSC, Bcl11a heterozygously deleted, biological rep3 |
| GSM2046011 |
HSC, Bcl11a homozygously deleted, biological rep1 |
| GSM2046012 |
HSC, Bcl11a homozygously deleted, biological rep2 |
| GSM2046013 |
HSC, Bcl11a homozygously deleted, biological rep3 |
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| Relations |
| BioProject |
PRJNA309701 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77207_RAW.tar |
73.6 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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