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

机译：造血干细胞生态位的鉴定和生态位大小的控制

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摘要

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). 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 embryogenesis. 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~- osteoblas-tic (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.
机译：造血干细胞（HSC）是骨髓细胞的一个子集，能够自我更新并形成所有类型的血细胞（多潜能）。然而，HSC的“利基” ——HSC所处的体内调节微环境-以及控制成年HSC数量的机制尚不清楚。骨形态发生蛋白（BMP）信号在胚胎发生过程中在诱导造血组织中起重要作用。我们通过分析具有条件的IA型BMP受体失活的突变小鼠（BMPRIA），研究了BMP信号通路在调节体内成年HSC发育中的作用。在这里，我们表明纺锤形的N-钙粘蛋白〜+ CD45〜-成骨细胞（SNO）细胞数量的增加与HSC数量的增加有关。发现长期HSC附着于SNO细胞。两个粘附的连接分子N-钙粘着蛋白和β-连环蛋白不对称地位于SNO细胞和长期HSC之间。我们得出的结论是，衬在骨表面的SNO细胞是支持HSC的利基的关键组成部分，并且通过BMPRIA的BMP信号传导通过调节利基大小来控制HSC的数量。

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