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Expression data from primitive and maturing hematopoietic stem cells

ABSTRACT: Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of stemness genes. The present study describes the construction and comparative molecular analysis of l-phage cDNA libraries from highly purified primitive HSCs (PHSCs) which retained their long term repopulating activities (LTRAs), and from maturing HSCs (MHSCs) which were largely depleted of LTRAs. Library inserts were amplified and tagged by a T7 RNA polymerase promoter and used to generate biotinylated cRNA for Microarray hybridization. Microarray analysis of the libraries confirmed previous results but also revealed an unforseen preferential expression of translation and metabolism associated genes in the PHSCs. Therefore these data indicate that HSCs are quiescent only in regard of proliferative activities, but are in a state of readiness to provide the metabolic and translational activities required following induction of proliferation by factors which induce differentiation and exit from the HSC pool. We used microarrays to detail the global programme of gene expression distinguishing primitive and maturing hematopoietic stem cells from mouse bone marrow and identified distinct classes of up- and down-regulated genes. Keywords: Adult hematopoietic stem cell populations

ORGANISM(S): Mus musculus

PROVIDER: GSE4391 | GEO | 2006/07/11

SECONDARY ACCESSION(S): PRJNA94579

REPOSITORIES: GEO

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Project description:In this study we investigated the effect of Slfn2 loss of function in the murine hematopoietic system. We chose to evaluate gene expression differences in multipotent progenitors, as this population was found to be diminshed in elektra homozygous mice, additionally the MPP population also displayed increased cell cycling compared to wildtype and increased apoptosis. Abstract from associated publication copied in below, from Warsi et al. 2022 Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells, published in Haematologica. DOI 10.3324/haematol.2021.279799 Even though hematopoietic stem cells (HSCs) are characterized by their ability to self-renew and differentiate, they primarily reside in quiescence. Despite the immense importance of this quiescent state, its maintenance and regulation is still incompletely understood. Schlafen2 (Slfn2) is a cytoplasmic protein known to be involved in cell proliferation, differentiation, quiescence, interferon response, and regulation of the immune system. Interestingly, Slfn2 is highly expressed in primitive hematopoietic cells. To investigate the role of Slfn2 in the regulation of HSCs we have studied HSC function in the elektra mouse model, where the elektra allele of the Slfn2 gene contains a point mutation causing loss of function of the Slfn2 protein. We found that homozygosity for the elektra allele caused a decrease of primitive hematopoietic compartments in murine bone marrow. We further found that transplantation of elektra bone marrow and purified HSCs resulted in a significantly reduced regenerative capacity of HSCs in competitive transplantation settings. Importantly, we found that a significantly higher fraction of elektra HSCs (as compared to WT HSCs) were actively cycling, suggesting that the mutation in Slfn2 increases HSC proliferation. This additionally caused an increased amount of apoptotic stem and progenitor cells. Taken together, our findings demonstrate that dysregulation of Slfn2 results in a functional deficiency of primitive hematopoietic cells, which is particularly reflected by a drastically impaired ability to reconstitute the hematopoietic system following transplantation and an increase in HSC proliferation. This study thus identifies Slfn2 as a novel and critical regulator of a dult HSCs and HSC quiescence.

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Expression data from primitive and maturing hematopoietic stem cells

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