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

doi: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

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

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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
Article number	e2338
Journal	PLoS ONE
Volume	3
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0002338
Publication status	Published - 4 Jun 2008

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© 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.

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A Novel Role for PECAM-1 (CD31) in Regulating Haematopoietic Progenitor CellFinal published version, 348 KBLicence: CC BY 3.0

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Ross, E. A., Freeman, S., Zhao, Y., Dhanjal, T. S., Ross, E. J., Lax, S., Ahmed, Z., Hou, T. Z., Kalia, N., Egginton, S., Nash, G., Watson, S. P., Frampton, J., & Buckley, C. D. (2008). A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow. PLoS ONE, 3(6), Article e2338. https://doi.org/10.1371/journal.pone.0002338

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

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.",

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

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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

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

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