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Publication : The Periostin/Integrin-αv Axis Regulates the Size of Hematopoietic Stem Cell Pool in the Fetal Liver.

First Author  Biswas A Year  2020
Journal  Stem Cell Reports Volume  15
Issue  2 Pages  340-357
PubMed ID  32735820 Mgi Jnum  J:311914
Mgi Id  MGI:6780886 Doi  10.1016/j.stemcr.2020.06.022
Citation  Biswas A, et al. (2020) The Periostin/Integrin-alphav Axis Regulates the Size of Hematopoietic Stem Cell Pool in the Fetal Liver. Stem Cell Reports 15(2):340-357
abstractText  We earlier showed that outside-in integrin signaling through POSTN-ITGAV interaction plays an important role in regulating adult hematopoietic stem cell (HSC) quiescence. Here, we show that Itgav deletion results in increased frequency of phenotypic HSCs in fetal liver (FL) due to faster proliferation. Systemic deletion of Postn led to increased proliferation of FL HSCs, albeit without any loss of stemness, unlike Vav-Itgav(-/-) HSCs. Based on RNA sequencing analysis of FL and bone marrow HSCs, we predicted the involvement of DNA damage response pathways in this dichotomy. Indeed, proliferative HSCs from Postn-deficient FL tissues showed increased levels of DNA repair, resulting in lesser double-strand breaks. Thus POSTN, with its expression majorly localized in the vascular endothelium of FL tissue, acts as a regulator of stem cell pool size during development. Overall, we demonstrate that the duality of response to proliferation in HSCs is developmental stage dependent and can be correlated with DNA damage responses.
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