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| Status |
Public on Mar 26, 2010 |
| Title |
GSK-3β inhibition promotes engraftment of ex vivo expanded hematopoietic stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Total RNA was isolated from three groups following expansion of CD34+ cells in cytokikes and then treatment with BIO, as described below.
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| Contributor(s) |
Ko K, Holmes T, Palladinetti P, Song E, Nordon R, O’Brien TA, Dolnikov A |
| Citation(s) |
22429797 |
| Submission date |
Mar 25, 2010 |
| Last update date |
Mar 23, 2020 |
| Contact name |
Kap-Hyoun Ko |
| E-mail(s) |
Kap-hyoun.Ko@SESIAHS.HEALTH.NSW.GOV.AU
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| Phone |
99870920
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| Organization name |
Sydney Children's Hospital
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| Department |
Cord and Marrow Transplant Facility
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| Lab |
Stem Cell Lab
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| Street address |
High Street
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| City |
Randwick |
| State/province |
NSW |
| ZIP/Postal code |
2031 |
| Country |
Australia |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA126741 |
