Bone marrow (BM) mesenchymal stem and progenitor cells (MSPCs) are a critical constituent of the hematopoietic stem cell (HSC) niche. Previous studies have suggested that the zinc-finger epithelial-mesenchymal transition transcription factor Snai2 (also known as Slug) regulated HSCs autonomously. Here, we show that Snai2 expression in the BM is restricted to the BM stromal compartment where it regulates the HSC niche. Germline or MSPC-selective Snai2 deletion reduces the functional MSPC pool and their mesenchymal lineage output and impairs HSC niche function during homeostasis and after stress. RNA sequencing analysis revealed that Spp1 (osteopontin) expression is markedly upregulated in Snai2-deficient MSPCs. Genetic deletion of Spp1 in Snai2-deficient mice rescues MSPCs’ functions. Thus, SNAI2 is a critical regulator of the transcriptional network maintaining MSPCs by the suppression of osteopontin expression.

骨髓（BM）间充质干细胞和祖细胞（MSPC）是造血干细胞（HSC）生态位的关键组成部分。先前的研究表明，锌指上皮-间质转化转录因子Snai2（也称为Slug）可自主调节HSC。在这里，我们显示BM中Snai2的表达仅限于BM基质区室，在这里它调节HSC的生态位。胚系或MSPC选择性Snai2缺失会降低功能性MSPC库及其间充质谱系输出，并在稳态和压力后损害HSC生态位功能。RNA测序分析显示Snai2中Spp1（骨桥蛋白）表达明显上调缺陷的MSPC。遗传缺失SPP1在SNAI2缺陷小鼠救援MSPCs'功能。因此，SNAI2是转录网络的关键调节因子，通过抑制骨桥蛋白的表达来维持MSPC。