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Title: Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis

Abstract

In the bone marrow cavity, hematopoietic stem cells (HSC) have been shown to reside in the endosteal and subendosteal perivascular niches, which play specific roles on HSC maintenance. Although cells with long-term ability to reconstitute full hematopoietic system can be isolated from both niches, several data support a heterogenous distribution regarding the cycling behavior of HSC. Whether this distinct behavior depends upon the role played by the stromal populations which distinctly create these two niches is a question that remains open. In the present report, we used our previously described in vivo assay to demonstrate that endosteal and subendosteal stromal populations are very distinct regarding skeletal lineage differentiation potential. This was further supported by a microarray-based analysis, which also demonstrated that these two stromal populations play distinct, albeit complementary, roles in HSC niche. Both stromal populations were preferentially isolated from the trabecular region and behave distinctly in vitro, as previously reported. Even though these two niches are organized in a very close range, in vivo assays and molecular analyses allowed us to identify endosteal stroma (F-OST) cells as fully committed osteoblasts and subendosteal stroma (F-RET) cells as uncommitted mesenchymal cells mainly represented by perivascular reticular cells expressing high levels ofmore » chemokine ligand, CXCL12. Interestingly, a number of cytokines and growth factors including interleukin-6 (IL-6), IL-7, IL-15, Hepatocyte growth factor (HGF) and stem cell factor (SCF) matrix metalloproteases (MMPs) were also found to be differentially expressed by F-OST and F-RET cells. Further microarray analyses indicated important mechanisms used by the two stromal compartments in order to create and coordinate the 'quiescent' and 'proliferative' niches in which hematopoietic stem cells and progenitors reside.« less

Authors:
 [1];  [2];  [3]; ; ;  [4]; ;  [5];  [6];  [5];  [2]
  1. School of Dentistry, Veiga de Almeida University, Rio de Janeiro, RJ (Brazil)
  2. Biomedical Science Institute, Federal University of Rio de Janeiro, Rio de Janeiro, RJ (Brazil)
  3. (United States)
  4. Department of Periodontics, Prevention and Geriatrics, University of Michigan School of Dentistry, Ann Arbor, MI (United States)
  5. National Institute on Aging, National Institute of Health, Baltimore, MD (United States)
  6. Instituto Oswaldo Cruz, Rio de Janeiro, RJ (Brazil)
Publication Date:
OSTI Identifier:
22212615
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 318; Journal Issue: 19; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD FORMATION; BONE MARROW; CAVITIES; CONNECTIVE TISSUE CELLS; IN VITRO; IN VIVO; LIGANDS; LYMPHOKINES; RETICULOENDOTHELIAL SYSTEM; STEM CELLS; TRABECULAR BONE

Citation Formats

Balduino, Alex, E-mail: balduino@uva.edu.br, Mello-Coelho, Valeria, National Institute on Aging, National Institute of Health, Baltimore, MD, Wang, Zhou, Taichman, Russell S., Krebsbach, Paul H., Weeraratna, Ashani T., Becker, Kevin G., Mello, Wallace de, Taub, Dennis D., and Borojevic, Radovan. Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis. United States: N. p., 2012. Web. doi:10.1016/J.YEXCR.2012.07.009.
Balduino, Alex, E-mail: balduino@uva.edu.br, Mello-Coelho, Valeria, National Institute on Aging, National Institute of Health, Baltimore, MD, Wang, Zhou, Taichman, Russell S., Krebsbach, Paul H., Weeraratna, Ashani T., Becker, Kevin G., Mello, Wallace de, Taub, Dennis D., & Borojevic, Radovan. Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis. United States. doi:10.1016/J.YEXCR.2012.07.009.
Balduino, Alex, E-mail: balduino@uva.edu.br, Mello-Coelho, Valeria, National Institute on Aging, National Institute of Health, Baltimore, MD, Wang, Zhou, Taichman, Russell S., Krebsbach, Paul H., Weeraratna, Ashani T., Becker, Kevin G., Mello, Wallace de, Taub, Dennis D., and Borojevic, Radovan. Thu . "Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis". United States. doi:10.1016/J.YEXCR.2012.07.009.
@article{osti_22212615,
title = {Molecular signature and in vivo behavior of bone marrow endosteal and subendosteal stromal cell populations and their relevance to hematopoiesis},
author = {Balduino, Alex, E-mail: balduino@uva.edu.br and Mello-Coelho, Valeria and National Institute on Aging, National Institute of Health, Baltimore, MD and Wang, Zhou and Taichman, Russell S. and Krebsbach, Paul H. and Weeraratna, Ashani T. and Becker, Kevin G. and Mello, Wallace de and Taub, Dennis D. and Borojevic, Radovan},
abstractNote = {In the bone marrow cavity, hematopoietic stem cells (HSC) have been shown to reside in the endosteal and subendosteal perivascular niches, which play specific roles on HSC maintenance. Although cells with long-term ability to reconstitute full hematopoietic system can be isolated from both niches, several data support a heterogenous distribution regarding the cycling behavior of HSC. Whether this distinct behavior depends upon the role played by the stromal populations which distinctly create these two niches is a question that remains open. In the present report, we used our previously described in vivo assay to demonstrate that endosteal and subendosteal stromal populations are very distinct regarding skeletal lineage differentiation potential. This was further supported by a microarray-based analysis, which also demonstrated that these two stromal populations play distinct, albeit complementary, roles in HSC niche. Both stromal populations were preferentially isolated from the trabecular region and behave distinctly in vitro, as previously reported. Even though these two niches are organized in a very close range, in vivo assays and molecular analyses allowed us to identify endosteal stroma (F-OST) cells as fully committed osteoblasts and subendosteal stroma (F-RET) cells as uncommitted mesenchymal cells mainly represented by perivascular reticular cells expressing high levels of chemokine ligand, CXCL12. Interestingly, a number of cytokines and growth factors including interleukin-6 (IL-6), IL-7, IL-15, Hepatocyte growth factor (HGF) and stem cell factor (SCF) matrix metalloproteases (MMPs) were also found to be differentially expressed by F-OST and F-RET cells. Further microarray analyses indicated important mechanisms used by the two stromal compartments in order to create and coordinate the 'quiescent' and 'proliferative' niches in which hematopoietic stem cells and progenitors reside.},
doi = {10.1016/J.YEXCR.2012.07.009},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 19,
volume = 318,
place = {United States},
year = {2012},
month = {11}
}