title: BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development.
abstract: Notch signaling plays a crucial role in controling the proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by theBloc1s2gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related complex (BORC).Bloc1s2-/-mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation ofbloc1s2in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking to control multiple stem and progenitor cell homeostasis in vertebrates.
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: University of Chinese Academy of Sciences, Beijing, China.|State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qiuping
authors.initials: Q
authors.lastname: He
authors.affiliation: University of Chinese Academy of Sciences, Beijing, China.|State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zongbin
authors.initials: Z
authors.lastname: Cui
authors.affiliation: University of Chinese Academy of Sciences, Beijing, China.|State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.|Center for Medical Genetics, Beijing Children's Hospital, Capital Medical University, Beijing, China.|Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China.|MOE Key Laboratory of Major Diseases in Children, Beijing, China.|Beijing Pediatric Research Institute, Beijing, China.
authors.forename: Wei
authors.identifier: 0000-0001-7430-6019
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008810:Mice, Inbred C57BL / Q000196:embryology; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology
chemical_list: C000603462:BLOS2 protein, mouse; D011506:Proteins; D051881:Receptor, Notch1
keywords: BLOS2; Notch; cell biology; developmental biology; endo-lysosomal trafficking; hematopoiesis; mouse; neurogenesis; stem and progenitor cell development; stem cells; zebrafish