Snai2 Maintains Bone Marrow Niche Cells by Repressing Osteopontin Expression

Dev Cell. 2020 Jun 8;53(5):503-513.e5. doi: 10.1016/j.devcel.2020.04.012. Epub 2020 May 14.

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.

Keywords: Snai2/Slug; bone marrow; hematopoietic stem cell niche; mesenchymal stem and progenitor cells; osteopontin/Spp1; self-renewal; stromal cells; transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cells, Cultured
  • Gene Deletion
  • Mice
  • Mice, Inbred C57BL
  • Osteopontin / genetics*
  • Osteopontin / metabolism
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism*
  • Stem Cell Niche*

Substances

  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Spp1 protein, mouse
  • Osteopontin