| Literature DB >> 32413329 |
Qiaozhi Wei1, Fumio Nakahara1, Noboru Asada1, Dachuan Zhang1, Xin Gao1, Chunliang Xu1, Alan Alfieri2, N Patrik Brodin2, Samuel E Zimmerman3, Jessica C Mar3, Chandan Guha4, Wenjun Guo1, Paul S Frenette5.
Abstract
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.Entities:
Keywords: Snai2/Slug; bone marrow; hematopoietic stem cell niche; mesenchymal stem and progenitor cells; osteopontin/Spp1; self-renewal; stromal cells; transcriptional regulation
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Year: 2020 PMID： 32413329 PMCID： PMC7299199 DOI： 10.1016/j.devcel.2020.04.012
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270