Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
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...
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| Published in | Nature (London) Vol. 466; no. 7308; pp. 829 - 834 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
12.08.2010
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| 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 β3 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.
A stem-cell niche made for two
The identity of the cells that form the haematopoietic stem-cell niche in the bone marrow has been unclear. Paul Frenette and colleagues have now identified nestin-expressing mesenchymal stem cells as niche-forming cells. These cells show a close physical association with haematopoietic stem cells, express high levels of genes involved in stem-cell maintenance, and their depletion reduces bone-marrow homing of haematopoietic progenitors. This work reveals the stem-cell niche in the bone marrow as a partnership between two distinct somatic stem-cell types.
The identity of the cells that form the haematopoietic stem cell (HSC) niche in bone marrow has been unclear. These authors identify nestin-expressing mesenchymal stem cells as niche-forming cells. These nestin-expressing cells show a close physical association with HSCs and express high levels of genes involved in HSC maintenance, and their depletion reduces bone marrow homing of haematopoietic progenitors. |
|---|---|
| AbstractList | 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. 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.+] 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.+] 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 β3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow [nestin.sup.+] cells and favours their osteoblastic differentiation, in vivo [nestin.sup.+] cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near [nestin.sup.+] MSCs in the bone marrow of lethally irradiated mice, whereas n vivo [nestin.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. 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 β3 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. A stem-cell niche made for two The identity of the cells that form the haematopoietic stem-cell niche in the bone marrow has been unclear. Paul Frenette and colleagues have now identified nestin-expressing mesenchymal stem cells as niche-forming cells. These cells show a close physical association with haematopoietic stem cells, express high levels of genes involved in stem-cell maintenance, and their depletion reduces bone-marrow homing of haematopoietic progenitors. This work reveals the stem-cell niche in the bone marrow as a partnership between two distinct somatic stem-cell types. The identity of the cells that form the haematopoietic stem cell (HSC) niche in bone marrow has been unclear. These authors identify nestin-expressing mesenchymal stem cells as niche-forming cells. These nestin-expressing cells show a close physical association with HSCs and express high levels of genes involved in HSC maintenance, and their depletion reduces bone marrow homing of haematopoietic progenitors. 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.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. 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 +^ 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 +^ 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 β3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin^sup +^ cells and favours their osteoblastic differentiation, in vivo nestin^sup +^ cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin^sup +^ MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin^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. [PUBLICATION 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 β3 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. |
| Audience | Academic |
| Author | Scadden, David T. Mazloom, Amin R. Ma’ayan, Avi Frenette, Paul S. MacArthur, Ben D. Michurina, Tatyana V. Ferraro, Francesca Lira, Sergio A. Méndez-Ferrer, Simón Enikolopov, Grigori N. |
| AuthorAffiliation | 3 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA 6 Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA 1 Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA 4 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA 5 Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA 2 Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA |
| AuthorAffiliation_xml | – name: 1 Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA – name: 3 Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA – name: 2 Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA – name: 4 Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA – name: 6 Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA – name: 5 Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York 10029, USA |
| Author_xml | – sequence: 1 givenname: Simón surname: Méndez-Ferrer fullname: Méndez-Ferrer, Simón email: simon.mendez-ferrer@cnic.es organization: Department of Medicine, Mount Sinai School of Medicine, Department of Gene and Cell Medicine, Mount Sinai School of Medicine, Present address: Department of Cardiovascular Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain (S.M.-F.); Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UK (B.D.M.) – sequence: 2 givenname: Tatyana V. surname: Michurina fullname: Michurina, Tatyana V. organization: Cold Spring Harbor Laboratory – sequence: 3 givenname: Francesca surname: Ferraro fullname: Ferraro, Francesca organization: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School – sequence: 4 givenname: Amin R. surname: Mazloom fullname: Mazloom, Amin R. organization: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine – sequence: 5 givenname: Ben D. surname: MacArthur fullname: MacArthur, Ben D. organization: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, Present address: Department of Cardiovascular Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain (S.M.-F.); Institute for Life Sciences, University of Southampton, Highfield, Southampton SO17 1BJ, UK (B.D.M.) – sequence: 6 givenname: Sergio A. surname: Lira fullname: Lira, Sergio A. organization: Department of Medicine, Mount Sinai School of Medicine – sequence: 7 givenname: David T. surname: Scadden fullname: Scadden, David T. organization: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School – sequence: 8 givenname: Avi surname: Ma’ayan fullname: Ma’ayan, Avi organization: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine – sequence: 9 givenname: Grigori N. surname: Enikolopov fullname: Enikolopov, Grigori N. organization: Cold Spring Harbor Laboratory – sequence: 10 givenname: Paul S. surname: Frenette fullname: Frenette, Paul S. email: paul.frenette@einstein.yu.edu organization: Department of Medicine, Mount Sinai School of Medicine, Department of Gene and Cell Medicine, Mount Sinai School of Medicine, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23074868$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/20703299$$D View this record in MEDLINE/PubMed |
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| Snippet | The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial... |
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| SubjectTerms | 631/136/142 631/136/232/1473/1542 631/136/532/2074 631/250/1620/1342 Animals Biological and medical sciences Bone marrow Bone marrow cells Cell Differentiation - drug effects Cell differentiation, maturation, development, hematopoiesis Cell Division Cell Lineage - drug effects Cell Movement Cell physiology Cells, Cultured Chemokine CXCL12 - metabolism Chondrocytes - cytology Chondrocytes - drug effects Fibers Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation - genetics Genetic aspects Granulocyte Colony-Stimulating Factor - pharmacology Hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - drug effects Hematopoietic Stem Cells - metabolism Humanities and Social Sciences Intermediate Filament Proteins - metabolism Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells - cytology Mesenchymal Stem Cells - drug effects Mesenchymal Stem Cells - metabolism Mice Mice, Transgenic Molecular and cellular biology multidisciplinary Multipotent Stem Cells - cytology Multipotent Stem Cells - drug effects Multipotent Stem Cells - metabolism Nerve Tissue Proteins - metabolism Nestin Osteoblasts Osteoblasts - cytology Osteoblasts - drug effects Osteoblasts - metabolism Parathyroid Hormone - pharmacology Physiological aspects Proteins Rodents Science Science (multidisciplinary) Stem Cell Niche - cytology Stem Cell Niche - drug effects Stem Cell Niche - metabolism Stem cells Stromal Cells - cytology Stromal Cells - drug effects Stromal Cells - metabolism Studies Sympathetic Nervous System - physiology |
| Title | Mesenchymal and haematopoietic stem cells form a unique bone marrow niche |
| URI | https://link.springer.com/article/10.1038/nature09262 https://www.ncbi.nlm.nih.gov/pubmed/20703299 https://www.proquest.com/docview/746437256 https://www.proquest.com/docview/748942418 https://pubmed.ncbi.nlm.nih.gov/PMC3146551 |
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