1. Cell Biology
  2. Stem Cells and Regenerative Medicine
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BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

  1. Wenwen Zhou
  2. Qiuping He
  3. Chunxia Zhang
  4. Xin He
  5. Zongbin Cui
  6. Feng Liu  Is a corresponding author
  7. Wei Li  Is a corresponding author
  1. Chinese Academy of Sciences, China
Research Article
  • Cited 17
  • Views 2,013
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Cite this article as: eLife 2016;5:e18108 doi: 10.7554/eLife.18108

Abstract

Notch signaling plays a crucial role in the control of proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1 related complex. 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 of bloc1s2 in 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 by controlling multiple stem and progenitor cell homeostasis in vertebrates.

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Author details

  1. Wenwen Zhou

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Qiuping He

    State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  3. Chunxia Zhang

    State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Xin He

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Zongbin Cui

    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Feng Liu

    State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
    For correspondence
    liuf@ioz.ac.cn
    Competing interests
    The authors declare that no competing interests exist.

  7. Wei Li

    State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    For correspondence
    wli@genetics.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7430-6019

Funding

National Natural Science Foundation of China (91539204)

  • Wei Li

National Natural Science Foundation of China (31230046)

  • Wei Li

National Natural Science Foundation of China (31471333)

  • Xin He

National Natural Science Foundation of China (31271570)

  • Feng Liu

Chinese Academy of Sciences (KJZD-EW-L08)

  • Wei Li

Ministry of Science and Technology of the People's Republic of China (2010CB945300)

  • Feng Liu

Chinese Academy of Sciences (XDA01010110)

  • Feng Liu

National Natural Science Foundation of China (31425016)

  • Feng Liu

Ministry of Science and Technology of the People's Republic of China (2011CB943900)

  • Feng Liu

National Natural Science Foundation of China (91332116)

  • Wei Li

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by the Institutional Animal Care and Use Committees of IGDB or IOZ, CAS (protocol number: KYD2006-002).

Reviewing Editor

  1. Amy J Wagers, Harvard University, United States

Publication history

  1. Received: May 23, 2016
  2. Accepted: October 4, 2016
  3. Accepted Manuscript published: October 10, 2016 (version 1)
  4. Version of Record published: November 3, 2016 (version 2)

Copyright

© 2016, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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