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Series GSE20282 Query DataSets for GSE20282
Status Public on Feb 02, 2011
Title Gfi1 regulates survival and lineage commitment of hematopoietic precursors and prevents myeloproliferative diseases
Organism Mus musculus
Experiment type Expression profiling by array
Summary Hematopoietic stem cells (HSCs) and lymphoid-primed multi-potential progenitors (LMPPs) are able to initiate both lymphoid and myeloid differentiation. We show here that the transcriptional repressor Gfi1 (growth factor independence 1) implements a specific gene expression program in HSCs and LMPPs that is critical for their survival and lymphoid differentiation potential. We present evidence that Gfi1 is required to maintain expression of genes involved in lymphoid development such as Flt-3, IL7R, Ebf1, Rag1, CCR9 and Notch1 and controls myeloid lineage commitment by regulating expression of genes such as Hoxa9 or M-CSFR. Gfi1 also inhibits apoptosis in HSCs by repressing pro-apoptotic genes such as Bax or Bak. As a consequence, Gfi1-/- mice show defects in self renewal, survival and both myeloid and lymphoid development of HSCs and LMPPs. Co-expression of a Bcl-2 transgene can partially restore the function of HSCs in Gfi1-/- mice, but not the defects in early lymphoid development. Of interest, Gfi1-/- x Bcl-2 transgenic mice show an accelerated expansion of myeloid cells and succumb to a fatal myeloproliferative disease resembling chronic myelomonocytic leukemia (CMML). Our data show that Gfi1 protects HSCs against apoptosis, ensures the proper development of LMPPs and plays a role in the development of myeloid leukemia.
We used microarrays to detail the global gene expression changes following knockout of Gfi1 in mouse LSK cells
Overall design We compared LSK cells isolated from Gfi1 knockout mice with wildtype cells to determine global gene expression changes by microarray analysis
Contributor(s) Klein-Hitpass L, Vassen L
Citation(s) 21732494
Submission date Feb 11, 2010
Last update date Jan 08, 2019
Contact name Ludger Klein-Hitpass
Phone +49 201 723 85552
Organization name Institut fuer Zellbiologie
Department Universitaetsklinikum
Lab BioChip Lab
Street address Virchowstr. 173
City Essen
ZIP/Postal code D-45122
Country Germany
Platforms (1)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
Samples (6)
GSM508528 5 Ko
GSM508529 7 Ko
GSM508530 8 Ko
BioProject PRJNA125313

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE20282_RAW.tar 56.5 Mb (http)(custom) TAR (of CEL, CHP)
Raw data provided as supplementary file
Processed data included within Sample table
Processed data provided as supplementary file

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