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

Abstract：

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Biswas A,Roy IM,Babu PC,Manesia J,Schouteden S,Vijayakurup V,Anto RJ,Huelsken J,Lacy-Hulbert A,Verfaillie CM,Khurana S

doi

10.1016/j.stemcr.2020.06.022

subject

Has Abstract

pub_date

2020-08-11 00:00:00

pages

340-357

issue

2

issn

2213-6711

pii

S2213-6711(20)30243-5

journal_volume

15

pub_type

杂志文章

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