|
| 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
|
| 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.
|
| |
|
| 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.
|
| |
|
| 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 |
| 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
|
| Organization name |
Brigham and Women's Hospital / Broad Institute of MIT and Harvard
|
| Department |
Hematology
|
| Lab |
Van Galen Lab
|
| Street address |
4 Blackfan Circle
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL14951 |
Illumina HumanHT-12 WG-DASL V4.0 R2 expression beadchip |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA194146 |
Less...
More...