학술논문
Cis inhibition of NOTCH1 through JAGGED1 sustains embryonic hematopoietic stem cell fate.
Document Type
Academic Journal
Author
Thambyrajah R; Program in Cancer Research. Institut Hospital del Mar d'Investigacions Mèdiques, CIBERONC, Barcelona, Spain. roshanathambyrajah@gmail.com.; Josep Carreras Leukemia Research Institute, Barcelona, Spain. roshanathambyrajah@gmail.com.; Centro de Investigacion Biomedica en Red (CIBER), Madrid, Spain. roshanathambyrajah@gmail.com.; Maqueda M; Program in Cancer Research. Institut Hospital del Mar d'Investigacions Mèdiques, CIBERONC, Barcelona, Spain.; Neo WH; Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.; Imbach K; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Guillén Y; Program in Cancer Research. Institut Hospital del Mar d'Investigacions Mèdiques, CIBERONC, Barcelona, Spain.; Grases D; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Fadlullah Z; Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.; Gambera S; Molecular Genetics of Angiogenesis Group. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Matteini F; Stem Cell Aging Group, Regenerative Medicine Program, The Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Program for advancing the Clinical Translation of Regenerative Medicine of Catalonia (P-CMR[C]), Barcelona, Spain.; Wang X; Department of Haematology, Wellcome - MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus, Cambridge, UK.; School of Public Health, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Calero-Nieto FJ; Department of Haematology, Wellcome - MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus, Cambridge, UK.; Esteller M; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Centro de Investigacion Biomedica en Red (CIBER), Madrid, Spain.; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.; Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain.; Florian MC; Centro de Investigacion Biomedica en Red (CIBER), Madrid, Spain.; Stem Cell Aging Group, Regenerative Medicine Program, The Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.; Program for advancing the Clinical Translation of Regenerative Medicine of Catalonia (P-CMR[C]), Barcelona, Spain.; Porta E; Josep Carreras Leukemia Research Institute, Barcelona, Spain.; Benedito R; Molecular Genetics of Angiogenesis Group. Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.; Göttgens B; Department of Haematology, Wellcome - MRC Cambridge Stem Cell Institute, Cambridge Biomedical Campus, Cambridge, UK.; Lacaud G; Cancer Research UK Stem Cell Biology Group, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, UK.; Espinosa L; Program in Cancer Research. Institut Hospital del Mar d'Investigacions Mèdiques, CIBERONC, Barcelona, Spain.; Centro de Investigacion Biomedica en Red (CIBER), Madrid, Spain.; Bigas A; Program in Cancer Research. Institut Hospital del Mar d'Investigacions Mèdiques, CIBERONC, Barcelona, Spain. abigas@researchmar.net.; Josep Carreras Leukemia Research Institute, Barcelona, Spain. abigas@researchmar.net.; Centro de Investigacion Biomedica en Red (CIBER), Madrid, Spain. abigas@researchmar.net.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
Hematopoietic stem cells (HSCs) develop from the hemogenic endothelium (HE) in the aorta- gonads-and mesonephros (AGM) region and reside within Intra-aortic hematopoietic clusters (IAHC) along with hematopoietic progenitors (HPC). The signalling mechanisms that distinguish HSCs from HPCs are unknown. Notch signaling is essential for arterial specification, IAHC formation and HSC activity, but current studies on how Notch segregates these different fates are inconsistent. We now demonstrate that Notch activity is highest in a subset of, GFI1 + , HSC-primed HE cells, and is gradually lost with HSC maturation. We uncover that the HSC phenotype is maintained due to increasing levels of NOTCH1 and JAG1 interactions on the surface of the same cell (cis) that renders the NOTCH1 receptor from being activated. Forced activation of the NOTCH1 receptor in IAHC activates a hematopoietic differentiation program. Our results indicate that NOTCH1-JAG1 cis-inhibition preserves the HSC phenotype in the hematopoietic clusters of the embryonic aorta.
(© 2024. The Author(s).)
(© 2024. The Author(s).)