biostudies-literatureChen YNatural Science Foundation of Zhejiang ProvinceNational Key Research and Development Program of China Stem Cell and Translational ResearchNational Natural Science Foundation of ChinaNHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China)National Key Research and Development Program of China, Stem Cell and Translational Researche12972https://www.ebi.ac.uk/biostudies/studies/S-EPMC7941224biostudies-literatureUnknown54(3)<h4>Objectives</h4>DNA damages pose threats to haematopoietic stem cells (HSC) maintenance and haematopoietic system homeostasis. Quiescent HSCs in adult mouse bone marrow are resistant to DNA damage, while human umbilical cord blood-derived proliferative HSCs are prone to cell death upon ionizing radiation. Murine embryonic HSCs proliferate in foetal livers and divide symmetrically to generate HSC pool. How murine embryonic HSCs respond to DNA damages is not well-defined.<h4>Materials and methods</h4>Mice models with DNA repair molecule Nbs1 or Nbs1/p53 specifically deleted in embryonic HSCs were generated. FACS analysis, in vitro and in vivo HSC differentiation assays, qPCR, immunofluorescence and Western blotting were used to delineate roles of Nbs1-p53 signaling in HSCs and haematopoieCell proliferationNbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis.PMC794122431770871815713802016YFA0100603KF2020005LY16H080009Wang ZQLi TJu ZChen YSun JfalseNbs1-mediated DNA damage repair pathway regulates haematopoietic stem cell development and embryonic haematopoiesis.<h4>Objectives</h4>DNA damages pose threats to haematopoietic stem cells (HSC) maintenance and haematopoietic system homeostasis. Quiescent HSCs in adult mouse bone marrow are resistant to DNA damage, while human umbilical cord blood-derived proliferative HSCs are prone to cell death upon ionizing radiation. Murine embryonic HSCs proliferate in foetal livers and divide symmetrically to generate HSC pool. How murine embryonic HSCs respond to DNA damages is not well-defined.<h4>Materials and methods</h4>Mice models with DNA repair molecule Nbs1 or Nbs1/p53 specifically deleted in embryonic HSCs were generated. FACS analysis, in vitro and in vivo HSC differentiation assays, qPCR, immunofluorescence and Western blotting were used to delineate roles of Nbs1-p53 signaling in HSCs and haematopoie2021-01-01T00:00:00Z2021 Mar2025-04-05T16:18:04.803Z2025-04-05T16:18:04.803ZS-EPMC79412243358624210.1111/cpr.12972