Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Nature. 2010 Aug 12;466(7308):829-34. doi: 10.1038/nature09262.

Abstract

The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Division
  • Cell Lineage / drug effects
  • Cell Movement
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Gene Expression Regulation / genetics
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Intermediate Filament Proteins / metabolism
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Transgenic
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / drug effects
  • Multipotent Stem Cells / metabolism
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Parathyroid Hormone / pharmacology
  • Stem Cell Niche / cytology*
  • Stem Cell Niche / drug effects
  • Stem Cell Niche / metabolism
  • Stromal Cells / cytology
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism
  • Sympathetic Nervous System / physiology

Substances

  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Parathyroid Hormone
  • Granulocyte Colony-Stimulating Factor

Associated data

  • GEO/GSE21941