PLX104914

GSE142705: Snai2 maintains bone marrow niche cells by repressing osteopontin expression

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

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, 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. SOURCE: Paul Frenette Albert Einstein College of Medicine