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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 11, 2013 |
| Title |
Gene expression analyses of hematopoietic stem cell (HSC) subsets in wildtype or CD41-KO mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The hematopoietic stem cell (HSC) compartment is heterogeneous, yet our understanding of the identities of different HSC subtypes is limited. Here we show that platelet integrin CD41 (αIIb), currently thought to only transiently mark fetal HSCs, is expressed on an adult HSC subtype that accumulates with age. CD41+ HSCs were largely quiescent and exhibited myeloerythroid and megakaryocyte gene priming, governed by Gata1, whereas CD41- HSCs were more proliferative and exhibited lymphoid gene priming. When isolated without the use of blocking antibodies, CD41+ HSCs possessed long-term repopulation capacity upon serial transplantations and showed a marked myeloid-bias compared to CD41-HSCs, which yielded a more lymphoid-biased progeny. CD41-knockout mice displayed multilineage hematopoietic defects coupled with decreased quiescence and survival of HSCs, suggesting that CD41 is functionally relevant for HSC maintenance and hematopoietic homeostasis. Transplantation experiments indicated that CD41-KO associated defects are long-term transplantable and HSC-derived, and in part mediated through the loss of platelet mass leading to decreases in HSC exposure to important platelet released cytokines, such as TGFβ1. In summary, our data provide a novel marker to identify a myeloid-biased HSC subtype that becomes prevalent with age, and highlights the dogma of HSC regulation by their progeny.
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| Overall design |
For microarray analysis, 1000 HSCs were FACS sorted from pools of 4-5 mice directly into lysis buffer, RNA extracted and whole transcript amplification was performed as previously described (Gonzalez-Roca E, Garcia-Albeniz X, Rodriguez-Mulero S, Gomis RR, Kornacker K, Auer H. Accurate expression profiling of very small cell populations. PLoS One. 2010;5:e14418.)
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| Contributor(s) |
Gekas C, Graf T |
| Citation(s) |
23564910 |
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| Submission date |
Mar 27, 2013 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Christos Gekas |
| E-mail(s) |
christos.gekas@gmail.com
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| Organization name |
Centre for Genomic Regulation (CRG)
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| Street address |
Carrer del Doctor Aiguader 88, Lab277
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| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA194578 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45561_RAW.tar |
210.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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