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Series GSE55237 Query DataSets for GSE55237
Status Public on Feb 01, 2015
Title Dendritic cell fate is determined by BCL11A
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage- specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed "default" pathway for common dendritic cell progenitors.
Overall design Raji cells were infected with retroviruses containing pXY-PURO (negative control vector) or pXY-BCL11A-XS. BJAB cells were infected with retroviruses containing pXY-PURO (negative control vector) or pXY-BCL11A-XL. Two arrays measured Raji BCL11A-XS expression and two arrays measured BJAB BCL11A-XL expression.
Citation(s) 24591644
Submission date Feb 21, 2014
Last update date Feb 25, 2015
Contact name Louis M. Staudt
Phone 301-402-1892
Organization name National Cancer Institute
Department Lymphoid Malignancies Branch
Lab Louis M Staudt
Street address 9000 Rockville Pike, Bldg 10, Rm 4N114
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (2)
GPL3278 NCI/Staudt human 15K v13
GPL18313 NCI/Staudt human 12K v10
Samples (4)
GSM1332253 BJAB BCL11A-XL - repeat 1 - mAdbID:25389
GSM1332254 BJAB BCL11A-XL - repeat 2 - mAdbID:26597
GSM1332255 Raji BCL11A-XS - repeat 1 - mAdbID:77951
BioProject PRJNA238980

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55237_RAW.tar 5.2 Mb (http)(custom) TAR (of GPR)
Raw data provided as supplementary file
Processed data included within Sample table
Raw data included within Sample table

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