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Series GSE33280 Query DataSets for GSE33280
Status Public on Jun 18, 2012
Title Gene regulation in hematopoietic cells by Pcgf1 in a Runx1 null background
Organism Mus musculus
Experiment type Expression profiling by array
Summary The transcription factor Runx1 is essential for the establishment of definitive hematopoiesis during embryonic development. In adult blood homeostasis, Runx1 plays a pivotal role in the maturation of lymphocytes and megakaryocytes. Furthermore, Runx1 is required for the regulation of hematopoietic stem and progenitor cell (HSPC) pools. However, how Runx1 orchestrates self-renewal and lineage choices in combination with other factors is not well understood. Here we describe a genome-scale RNAi screen to detect genes that cooperate with Runx1 in regulating HSPCs. We identify the polycomb group protein Pcgf1 as an epigenetic regulator involved in hematopoietic cell differentiation. We show that simultaneous depletion of Runx1 and Pcgf1 allows sustained self-renewal while blocking differentiation of HSPCs in vitro. We find an upregulation of HoxA cluster genes upon Pcgf1 knockdown that possibly accounts for the increase in self-renewal. Further, our data suggest that cells lacking both Runx1 and Pcgf1 are blocked at an early progenitor stage, indicating that a concerted action of the transcription factor Runx1 together with the epigenetic repressor Pcgf1 is necessary for terminal differentiation. Thus, our work discovers a genetic link between transcriptional and epigenetic regulation that is required for hematopoietic differentiation.
 
Overall design Hematopoietic stem and precursor cells freshly isolated from mice were transduced with an shRNA targeting Pcgf1 or a control shRNA. Cells were selected with puromycin for 36 h before total mRNA was isolated.
 
Contributor(s) Sedello AK, Jarrells J, Paszkowski-Rogacz M, Ross K, Buchholz F
Citation(s) 22411870
Submission date Oct 27, 2011
Last update date Jan 12, 2017
Contact name Maciej Paszkowski-Rogacz
Organization name Technische Universit├Ąt Dresden
Department UCC / Medical Faculty and University Hospital Carl Gustav Carus
Lab Medical Systems Biology (Prof. Buchholz)
Street address Tatzberg 47/49
City Dresden
ZIP/Postal code 01307
Country Germany
 
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (8)
GSM823370 mouse 1 Control shRNA
GSM823371 mouse 1 Pcgf1 shRNA
GSM823372 mouse 2 Control shRNA
Relations
BioProject PRJNA149081

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
GSE33280_RAW.tar 15.4 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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