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GSK-3β inhibition promotes engraftment of ex vivo expanded hematopoietic stem cells

ABSTRACT: Glycogen synthase kinase-3β (GSK-3β) has been recently identified as an important regulator of stem cell function. In vitro studies show that GSK-3β inhibition delays proliferation of human haematopoietic progenitor cells while increasing numbers of late dividing multipotent progenitors. Gene expression analysis revealed that GSK-3β inhibition modulates the expression of a subset of genes that are transcriptional targets for cytokines. GSK-3β inhibition antagonised down-regulation of genes encoding cyclin dependent kinase inhibitor p57 and a member of the growth arrest and DNA damage 45 family, GADD45B as well as up-regulation of cyclin D1 by cytokines, providing a possible mechanism for the BIO-induced delay in cell cycle progression. Surprisingly, inhibition of GSK-3β earlier shown to prevent β-catenin degradation and promote the nuclear accumulation of β-catenin was not sufficient to activate its transcriptional targets in haematopoietic stem cells. GSK-3β inhibition up-regulated the expression of a several positive regulators of stem cell function suppressed during cytokine-induced proliferation. The data supports a clinical role for GSK-3β inhibition to improve engraftment efficiency of ex vivo expanded stem cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE21073 | GEO | 2010/03/26

SECONDARY ACCESSION(S): PRJNA126741

REPOSITORIES: GEO

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| PRJNA717225 | ENA

Homo sapiens

Project description:GSK-3β inhibition promotes engraftment of ex vivo expanded hematopoietic stem cells

| PRJNA126741 | ENA

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