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.
•Snai2 is required for bone marrow MSPC maintenance and regeneration•Snai2 deletion compromises the HSC niche during homeostasis and after stress•Snai2 suppresses osteopontin (Spp1) expression in MSPCs•Compound Snai2 and Spp1 knockouts rescue MSPC function
Wei et al. found that Snai2 is preferentially expressed and required in bone marrow mesenchymal stem and progenitor cells (MSPCs) for their maintenance and regeneration. The authors show that Snai2 promotes self-renewal by suppressing Spp1 expression in MSPCs.