TGF-β Signaling Plays an Essential Role in the Lineage Specification of Mesenchymal Stem/Progenitor Cells in Fetal Bone Marrow

Stem Cell Reports. 2019 Jul 9;13(1):48-60. doi: 10.1016/j.stemcr.2019.05.017. Epub 2019 Jun 13.

Abstract

Mesenchymal stromal cells are key components of hematopoietic niches in the bone marrow. Here we abrogated transforming growth factor β (TGF-β) signaling in mesenchymal stem/progenitor cells (MSPCs) by deleting Tgfbr2 in mesenchymal cells using a doxycycline-repressible Sp7 (osterix)-Cre transgene. We show that loss of TGF-β signaling during fetal development results in a marked expansion of CXCL12-abundant reticular (CAR) cells and adipocytes in the bone marrow, while osteoblasts are significantly reduced. These stromal alterations are associated with significant defects in hematopoiesis, including a shift from lymphopoiesis to myelopoiesis. However, hematopoietic stem cell function is preserved. Interestingly, TGF-β signaling is dispensable for the maintenance of mesenchymal cells in the bone marrow after birth under steady-state conditions. Collectively, these data show that TGF-β plays an essential role in the lineage specification of fetal but not definitive MSPCs and is required for the establishment of normal hematopoietic niches in fetal and perinatal bone marrow.

Keywords: CAR cells; adipocyte; and osteoblast; bone marrow niche; bone metabolism; hematopoiesis; lineage commitment; mesenchymal stem cells; transforming growth factor β.

Publication types

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

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / metabolism
  • Cell Differentiation*
  • Cell Line
  • Cell Lineage*
  • Gene Deletion
  • Hematopoiesis
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Receptor, Transforming Growth Factor-beta Type II / genetics
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*

Substances

  • Transforming Growth Factor beta
  • Receptor, Transforming Growth Factor-beta Type II