Role of Chk1 in the differentiation program of hematopoietic stem cells
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Hematopoietic stem cells (HSC) isolated from umbilical cord blood (UCB) were treated with ionizing radiation (IR) and sensitivity and IR induced checkpoints activation were investigated. No difference in the sensitivity and in the activation of DNA damage pathways was observed between CD133+ HSC and cells derived from them after ex vivo expansion. Chk1 protein was very low in freshly isolated CD133+ cells, and undetectable in ex vivo expanded UCB CD133+ cells. Chk1 was expressed only on day 3 of the ex vivo expansion. This pattern of Chk1 expression was corroborated in CD133+ cells isolated from peripheral blood apheresis collected from an healthy donor. Treatment with a specific Chk1 inhibitor resulted in a strong reduction in the percentage of myeloid precursors (CD33+) and an increase in the percentage of lymphoid precursors (CD38+) compared to untreated cells, suggesting a possible role for Chk1 in the differentiation program of UCB CD133+ HSC.
KeywordsStem and progenitor cells Umbilical cord blood Chk1 DNA damage Differentiation
We thank Dr Patrick Casara and Dr John Hickman who respectively synthesized and kindly provided the Chk1 inhibitor compound. A special thank to JD Baggott that kindly edited the paper. This study was supported by grants from “Fondazione I1 Sangue”, Ministero della Salute, Istituto Superiore di Sanità, Sixth FP “Thercord”, Foundation Novussanguis and Jérome Lejeune. The generous contribution of the Italian Association for Cancer Research and of FIRB is also gratefully acknowledged.
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