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Identification of the haematopoietic stem cell niche and control of the niche size

Author

Listed:
  • Jiwang Zhang

    (Stowers Institute for Medical Research)

  • Chao Niu

    (Stowers Institute for Medical Research)

  • Ling Ye

    (School of Dentistry, University of Missouri–Kansas City)

  • Haiyang Huang

    (School of Dentistry, University of Missouri–Kansas City)

  • Xi He

    (Stowers Institute for Medical Research)

  • Wei-Gang Tong

    (Stowers Institute for Medical Research)

  • Jason Ross

    (Stowers Institute for Medical Research)

  • Jeff Haug

    (Stowers Institute for Medical Research)

  • Teri Johnson

    (Stowers Institute for Medical Research)

  • Jian Q. Feng

    (School of Dentistry, University of Missouri–Kansas City)

  • Stephen Harris

    (School of Dentistry, University of Missouri–Kansas City)

  • Leanne M. Wiedemann

    (Stowers Institute for Medical Research
    Kansas University Medical Center)

  • Yuji Mishina

    (National Institute of Environmental Health Sciences, Research Triangle Park)

  • Linheng Li

    (Stowers Institute for Medical Research
    Kansas University Medical Center)

Abstract

Haematopoietic stem cells (HSCs) are a subset of bone marrow cells that are capable of self-renewal and of forming all types of blood cells (multi-potential)1. However, the HSC ‘niche’—the in vivo regulatory microenvironment where HSCs reside—and the mechanisms involved in controlling the number of adult HSCs remain largely unknown. The bone morphogenetic protein (BMP) signal has an essential role in inducing haematopoietic tissue during embryogenesis2,3. We investigated the roles of the BMP signalling pathway in regulating adult HSC development in vivo by analysing mutant mice with conditional inactivation of BMP receptor type IA (BMPRIA). Here we show that an increase in the number of spindle-shaped N-cadherin+CD45- osteoblastic (SNO) cells correlates with an increase in the number of HSCs. The long-term HSCs are found attached to SNO cells. Two adherens junction molecules, N-cadherin and β-catenin, are asymmetrically localized between the SNO cells and the long-term HSCs. We conclude that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of HSCs by regulating niche size.

Suggested Citation

  • Jiwang Zhang & Chao Niu & Ling Ye & Haiyang Huang & Xi He & Wei-Gang Tong & Jason Ross & Jeff Haug & Teri Johnson & Jian Q. Feng & Stephen Harris & Leanne M. Wiedemann & Yuji Mishina & Linheng Li, 2003. "Identification of the haematopoietic stem cell niche and control of the niche size," Nature, Nature, vol. 425(6960), pages 836-841, October.
    • Handle: RePEc:nat:nature:v:425:y:2003:i:6960:d:10.1038_nature02041
    DOI: 10.1038/nature02041
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    Cited by:

    1. Adrienne Anginot & Julie Nguyen & Zeina Abou Nader & Vincent Rondeau & Amélie Bonaud & Maria Kalogeraki & Antoine Boutin & Julia P. Lemos & Valeria Bisio & Joyce Koenen & Lea Hanna Doumit Sakr & Amand, 2023. "WHIM Syndrome-linked CXCR4 mutations drive osteoporosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Xue Zhong & Nagesh Peddada & Jianhui Wang & James J. Moresco & Xiaowei Zhan & John M. Shelton & Jeffrey A. SoRelle & Katie Keller & Danielle Renee Lazaro & Eva Marie Y. Moresco & Jin Huk Choi & Bruce , 2023. "OVOL2 sustains postnatal thymic epithelial cell identity," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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