A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow

Ewan A. Ross*, Sylvie Freeman, Yan Zhao, Tarvinder S. Dhanjal, Emma J. Ross, Sian Lax, Zubair Ahmed, Tie Zheng Hou, Neena Kalia, Stuart Egginton, Gerard Nash, Steven P. Watson, Jon Frampton, Christopher D. Buckley

*Corresponding author for this work

Research output: Contribution to journalArticle

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 languageEnglish
Article numbere2338
JournalPLoS ONE
Volume3
Issue number6
DOIs
Publication statusPublished - 4 Jun 2008

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CD31 Antigens
Hematopoietic Stem Cells
bone marrow
Bone
Blood
Bone Marrow
Blood Vessels
blood vessels
blood
Stem cells
niches
Cell Count
Chemokine CXCL12
Adoptive Transfer
gelatinase B
Matrix Metalloproteinases
Bone Marrow Cells
Cell Movement
hematopoietic stem cells
cell movement

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

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. / A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow. In: PLoS ONE. 2008 ; Vol. 3, No. 6.
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Ross, EA, Freeman, S, Zhao, Y, Dhanjal, TS, Ross, EJ, Lax, S, Ahmed, Z, Hou, TZ, Kalia, N, Egginton, S, Nash, G, Watson, SP, Frampton, J & Buckley, CD 2008, 'A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow', PLoS ONE, vol. 3, no. 6, e2338. https://doi.org/10.1371/journal.pone.0002338

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 journalArticle

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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.

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