E-GEOD-45486 - Human hematopoietic stem cell expansion through modulation of lineage-associated gene expression programs

Status
Released on 1 December 2013, last updated on 3 June 2014
Organism
Homo sapiens
Samples (6)
Array (1)
Protocols (12)
Description
Hematopoietic stem cells (HSCs) must balance self-renewal and lineage differentiation to regenerate the hematopoietic system throughout life. HSCs exhibit lineage-associated gene expression that keeps them responsive to demands of mature blood production. However, it is not known whether this process, termed lineage priming, directly influences HSC self-renewal. We investigated the link between stemness and lineage priming by attenuating the early lymphoid transcription factor E47 through ID2 over-expression (OE). Transcriptional profiling of ID2 OE HSCs showed down regulation of B-cell factors including EBF1 and FOXO1 with a concomitant increase in stemness programs and myeloerythroid factors including CEBPA and GATA1. This resulted in myeloid commitment bias from the earliest stages of differentiation. HSC self-renewal was strongly affected by this lineage perturbation resulting in an 11-fold expansion of HSCs. Thus, early lymphoid transcription factors antagonize human HSC self-renewal, providing a direct link between differentiation program priming and the maintenance of stem cell self-renewal. Three independent lineage depleted CB samples were transduced with P-CTRL or P-ID2 and injected into 5 mice (30 mice total). From every group of 5 mice, human lin- cells were isolated and GFP+CD34+CD38-CD45RA- HSPCs were sorted by FACS.
Experiment type
transcription profiling by array 
Contacts
Antonija Kreso, Craig April, Elisa Laurenti, Eric Lechman, Erno Wienholds, Jian-Bing Fan, John E Dick, Kolja Eppert, Nathan Mbong, Peter van Galen
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-45486.idf.txt
Sample and data relationshipE-GEOD-45486.sdrf.txt
Processed data (1)E-GEOD-45486.processed.1.zip
Array designA-GEOD-14951.adf.txt
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