Dataset Information


The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells

ABSTRACT: 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. 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.

ORGANISM(S): Mus musculus  

SUBMITTER: R K Humphries   Connie J Eaves  Heidi Mader  David G Kent  Keegan Rowe  Claudia Benz  Sonja Babovic  Stefan Wohrer  Connie Eaves  David J Knapp  David Q Treloar  Philip A Beer  Michael R Copley  Christopiher Day  Florian Kuchenbauer 

PROVIDER: E-GEOD-41758 | ArrayExpress | 2013-06-27



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