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

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 and Linheng Li ()
Additional contact information
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
Yuji Mishina: National Institute of Environmental Health Sciences, Research Triangle Park
Linheng Li: Stowers Institute for Medical Research

Nature, 2003, vol. 425, issue 6960, 836-841

Abstract: 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.

Date: 2003
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DOI: 10.1038/nature02041

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