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Status |
Public on Dec 01, 2013 |
Title |
Reduced lymphoid lineage priming promotes human hematopoietic stem cell expansion |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
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.
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Contributor(s) |
van Galen P, Kreso A, Wienholds E, Laurenti E, Eppert K, Lechman E, Mbong N, April C, Fan J, Dick JE |
Citation(s) |
24388174 |
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Submission date |
Mar 25, 2013 |
Last update date |
Dec 22, 2017 |
Contact name |
Peter van Galen |
E-mail(s) |
petervangalen@gmail.com, pvangalen@bwh.harvard.edu
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Organization name |
Brigham and Women's Hospital / Broad Institute of MIT and Harvard
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Department |
Hematology
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Lab |
Van Galen Lab
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Street address |
4 Blackfan Circle
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City |
Boston |
State/province |
Massachusetts |
ZIP/Postal code |
02115 |
Country |
USA |
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Platforms (1) |
GPL14951 |
Illumina HumanHT-12 WG-DASL V4.0 R2 expression beadchip |
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Samples (6)
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Relations |
BioProject |
PRJNA194146 |