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| Status |
Public on Jun 27, 2013 |
| Title |
The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mouse haematopoietic stem cells (HSCs) undergo a post-natal transition in several properties, including a marked reduction in their self-renewal activity. We now show that the developmentally timed change in this key function of HSCs is associated with their decreased expression of Lin28b and an accompanying increase in their let-7 microRNA levels. Lentivirus(LV)-mediated overexpression of Lin28 in adult HSCs elevates their self-renewal activity in transplanted irradiated hosts, as does overexpression of Hmga2, a well-established let-7 target that is upregulated in fetal HSCs. Conversely, HSCs from fetal Hmga2-/- mice do not display the heightened self-renewal activity that is characteristic of wild-type fetal HSCs. Interestingly, overexpression of Hmga2 in adult HSCs does not mimic the ability of elevated Lin28 to activate a fetal lymphoid differentiation program. Thus Lin28b may act as a master regulator of developmentally timed changes in HSC programs with Hmga2 serving as its specific downstream modulator of HSC self-renewal potential.
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| Overall design |
Lin-Sca1+cKit+ cells were isolated from E14.5 fetal livers (of wild-type of Hmga2-/- embryos) or the bone marrow of 8-12 week old mice by fluorescence activated cell sorting. The RNA was extracted and hybridized on Affymetrix mpuse gene 1.0 ST microarrays.
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| Contributor(s) |
Copley MR, Babovic S, Benz C, Knapp DJ, Beer PA, Kent DG, Wohrer S, Treloar DQ, Day C, Rowe K, Mader H, Kuchenbauer F, Humphries RK, Eaves CJ |
| Citation(s) |
23811688 |
| Submission date |
Oct 22, 2012 |
| Last update date |
Nov 04, 2015 |
| Contact name |
Connie Eaves |
| E-mail(s) |
ceaves@bccrc.ca
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| Phone |
604-675-8122
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| Organization name |
BC Cancer Agency
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| Department |
Terry Fox Laboratory
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| Street address |
675 West 10th Avenue
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z1L3 |
| Country |
Canada |
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| Platforms (1) |
| GPL10740 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [probe set (exon) version] |
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| Samples (8)
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| GSM1023629 |
Fetal liver HSCs/progenitors (Hmga2+/+), biological replicate 1 |
| GSM1023630 |
Fetal liver HSCs/progenitors (Hmga2+/+), biological replicate 2 |
| GSM1023631 |
Fetal liver HSCs/progenitors (Hmga2+/+), biological replicate 3 |
| GSM1023632 |
Fetal liver HSCs/progenitors (Hmga2-/-), biological replicate 1 |
| GSM1023633 |
Fetal liver HSCs/progenitors (Hmga2-/-), biological replicate 2 |
| GSM1023634 |
Fetal liver HSCs/progenitors (Hmga2-/-), biological replicate 3 |
| GSM1023635 |
Adult bone marrow HSCs/progenitors (Hmga2+/+), biological replicate 1 |
| GSM1023636 |
Adult bone marrow HSCs/progenitors (Hmga2+/+), biological replicate 2 |
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| Relations |
| BioProject |
PRJNA178115 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE41758_Data_by_Exon_IDs.txt.gz |
5.8 Mb |
(ftp)(http) |
TXT |
| GSE41758_RAW.tar |
31.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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