Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression.

Qiaozhi Wei, Fumio Nakahara, Noboru Asada, Dachuan Zhang, Xin Gao, Chunliang Xu, Alan Alfieri, N Patrik Brodin, Samuel E Zimmerman, Jessica C Mar, Chandan Guha, Wenjun Guo, Paul S Frenette

Developmental cell 2020 Jun 08

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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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Qiaozhi Wei, Fumio Nakahara, Noboru Asada, Dachuan Zhang, Xin Gao, Chunliang Xu, Alan Alfieri, N Patrik Brodin, Samuel E Zimmerman, Jessica C Mar, Chandan Guha, Wenjun Guo, Paul S Frenette. Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression. Developmental cell. 2020 Jun 08;53(5):503-513.e5