Abstract
Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor number in the peripheral blood but not the bone marrow compartment PECAM-1-/- is required on both progenitors and bone marrow vascular cels in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1-/- bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. The findings suggest a novel role for a PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the blood.
Original language | English |
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Article number | e2338 |
Journal | PLoS ONE |
Volume | 3 |
Issue number | 6 |
DOIs | |
Publication status | Published - 4 Jun 2008 |
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Bibliographical note
© 2008 Ross et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Cite this
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A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow. / Ross, Ewan A.; Freeman, Sylvie; Zhao, Yan; Dhanjal, Tarvinder S.; Ross, Emma J.; Lax, Sian; Ahmed, Zubair; Hou, Tie Zheng; Kalia, Neena; Egginton, Stuart; Nash, Gerard; Watson, Steven P.; Frampton, Jon; Buckley, Christopher D.
In: PLoS ONE, Vol. 3, No. 6, e2338, 04.06.2008.Research output: Contribution to journal › Article
TY - JOUR
T1 - A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow
AU - Ross, Ewan A.
AU - Freeman, Sylvie
AU - Zhao, Yan
AU - Dhanjal, Tarvinder S.
AU - Ross, Emma J.
AU - Lax, Sian
AU - Ahmed, Zubair
AU - Hou, Tie Zheng
AU - Kalia, Neena
AU - Egginton, Stuart
AU - Nash, Gerard
AU - Watson, Steven P.
AU - Frampton, Jon
AU - Buckley, Christopher D.
N1 - © 2008 Ross et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2008/6/4
Y1 - 2008/6/4
N2 - Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor number in the peripheral blood but not the bone marrow compartment PECAM-1-/- is required on both progenitors and bone marrow vascular cels in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1-/- bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. The findings suggest a novel role for a PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the blood.
AB - Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor number in the peripheral blood but not the bone marrow compartment PECAM-1-/- is required on both progenitors and bone marrow vascular cels in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1-/- bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. The findings suggest a novel role for a PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the blood.
UR - http://www.scopus.com/inward/record.url?scp=48649084227&partnerID=8YFLogxK
UR - https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002338
U2 - 10.1371/journal.pone.0002338
DO - 10.1371/journal.pone.0002338
M3 - Article
C2 - 18523558
AN - SCOPUS:48649084227
VL - 3
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 6
M1 - e2338
ER -