Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Simón Méndez-Ferrer, Tatyana V. Michurina, Francesca Ferraro, Amin R. Mazloom, Ben D. MacArthur, Sergio A. Lira, David T. Scadden, Avi Mag'Ayan, Grigori N. Enikolopov, Paul S. Frenette

Research output: Contribution to journalArticle

1846 Citations (Scopus)

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 γ 23 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.

Original languageEnglish (US)
Pages (from-to)829-834
Number of pages6
JournalNature
Volume466
Issue number7308
DOIs
StatePublished - Aug 12 2010

Fingerprint

Nestin
Hematopoietic Stem Cells
Mesenchymal Stromal Cells
Bone Marrow
Stem Cell Niche
Stem Cells
Hematopoietic Stem Cell Mobilization
Adrenergic Fibers
Adult Stem Cells
Cellular Structures
Parathyroid Hormone
Osteoblasts
Nerve Fibers
Bone Marrow Cells
Genes
Down-Regulation
Endothelial Cells
Transplantation
Maintenance

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Méndez-Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., ... Frenette, P. S. (2010). Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 466(7308), 829-834. https://doi.org/10.1038/nature09262

Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. / Méndez-Ferrer, Simón; Michurina, Tatyana V.; Ferraro, Francesca; Mazloom, Amin R.; MacArthur, Ben D.; Lira, Sergio A.; Scadden, David T.; Mag'Ayan, Avi; Enikolopov, Grigori N.; Frenette, Paul S.

In: Nature, Vol. 466, No. 7308, 12.08.2010, p. 829-834.

Research output: Contribution to journalArticle

Méndez-Ferrer, S, Michurina, TV, Ferraro, F, Mazloom, AR, MacArthur, BD, Lira, SA, Scadden, DT, Mag'Ayan, A, Enikolopov, GN & Frenette, PS 2010, 'Mesenchymal and haematopoietic stem cells form a unique bone marrow niche', Nature, vol. 466, no. 7308, pp. 829-834. https://doi.org/10.1038/nature09262
Méndez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, MacArthur BD, Lira SA et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010 Aug 12;466(7308):829-834. https://doi.org/10.1038/nature09262
Méndez-Ferrer, Simón ; Michurina, Tatyana V. ; Ferraro, Francesca ; Mazloom, Amin R. ; MacArthur, Ben D. ; Lira, Sergio A. ; Scadden, David T. ; Mag'Ayan, Avi ; Enikolopov, Grigori N. ; Frenette, Paul S. / Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. In: Nature. 2010 ; Vol. 466, No. 7308. pp. 829-834.
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