Mesenchymal and haematopoietic stem cells form a unique bone marrow niche

Méndez-Ferrer, S., Michurina, T. V., Ferraro, F., Mazloom, A. R., MacArthur, B. D., Lira, S. A., Scadden, D. T., Mag'Ayan, A., Enikolopov, G. N., Frenette, P. S. (August 2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature, 466 (7308). pp. 829-834.

DOI: 10.1038/nature09262


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 <sup>+</sup> 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 <sup>+</sup> 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 <sup>+</sup> cells and favours their osteoblastic differentiation, in vivo nestin <sup>+</sup> cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin <sup>+</sup> MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin <sup>+</sup> 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. © 2010 Macmillan Publishers Limited. All rights reserved.

Item Type: Paper
Subjects: therapies > stem cells
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: CSHL Librarian
Date: 12 August 2010
Date Deposited: 03 Oct 2011 16:22
Last Modified: 30 Dec 2014 17:04
PMCID: PMC3146551
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