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nature portfolio permissions reprints spindle-shaped n-cadherin+cd45- osteoblastic privacy policy manuscript editing providing anti-bmpr1a anti-serum research triangle park de-cadherin-mediated cell adhesion advertising medical research scientific discussion subscribe nature social media author information authors nature 404 nature 414 nature 425 nature author correspondence pkh-labeled hematopoietic cells spleen colony-forming cell springerlink instant access permissions long-term repopulating subset haematopoietic stem cell haematopoietic stem cells hematopoietic stem cell development supplementary data 2a supplementary data 2b supplementary data methods bone morphogenetic protein bone morphogenetic protein-2 hematopoietic stem cells mesenchymal precursor cells osteoblastic cells regulate follicular stem cells stem cells find haemopoietic stem cells stem cell niches privacy wiedemann & linheng li bone marrow cells mouse bone marrow inducing haematopoietic tissue receptor type ib cell cycle kinetics competing financial interests bone marrow niche regulating niche size

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         description: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.
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