Cargando…

Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment

Lysophosphatidic acid (LPA) is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during norma...

Descripción completa

Detalles Bibliográficos
Autores principales: Evseenko, Denis, Latour, Brooke, Richardson, Wade, Corselli, Mirko, Sahaghian, Arineh, Cardinal, Sofie, Zhu, Yuhua, Chan, Rebecca, Dunn, Bruce, Crooks, Gay M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655943/
https://www.ncbi.nlm.nih.gov/pubmed/23696850
http://dx.doi.org/10.1371/journal.pone.0063718
_version_ 1782269953599078400
author Evseenko, Denis
Latour, Brooke
Richardson, Wade
Corselli, Mirko
Sahaghian, Arineh
Cardinal, Sofie
Zhu, Yuhua
Chan, Rebecca
Dunn, Bruce
Crooks, Gay M.
author_facet Evseenko, Denis
Latour, Brooke
Richardson, Wade
Corselli, Mirko
Sahaghian, Arineh
Cardinal, Sofie
Zhu, Yuhua
Chan, Rebecca
Dunn, Bruce
Crooks, Gay M.
author_sort Evseenko, Denis
collection PubMed
description Lysophosphatidic acid (LPA) is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during normal human hematopoiesis. In vitro stimulation of CD34+ human hematopoietic progenitors by LPA induced myeloid differentiation but had no effect on lymphoid differentiation. LPA receptors were expressed at significantly higher levels on Common Myeloid Progenitors (CMP) than either multipotent Hematopoietic Stem/Progenitor Cells (HSPC) or Common Lymphoid Progenitors (CLP) suggesting that LPA acts on committed myeloid progenitors. Functional studies demonstrated that LPA enhanced migration, induced cell proliferation and reduced apoptosis of isolated CMP, but had no effect on either HSPC or CLP. Analysis of adult and fetal human bone marrow sections showed that PPAP2A, (the enzyme which degrades LPA) was highly expressed in the osteoblastic niche but not in the perivascular regions, whereas Autotaxin (the enzyme that synthesizes LPA) was expressed in perivascular regions of the marrow. We propose that a gradient of LPA with the highest levels in peri-sinusoidal regions and lowest near the endosteal zone, regulates the localization, proliferation and differentiation of myeloid progenitors within the bone marrow marrow.
format Online
Article
Text
id pubmed-3655943
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-36559432013-05-21 Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment Evseenko, Denis Latour, Brooke Richardson, Wade Corselli, Mirko Sahaghian, Arineh Cardinal, Sofie Zhu, Yuhua Chan, Rebecca Dunn, Bruce Crooks, Gay M. PLoS One Research Article Lysophosphatidic acid (LPA) is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during normal human hematopoiesis. In vitro stimulation of CD34+ human hematopoietic progenitors by LPA induced myeloid differentiation but had no effect on lymphoid differentiation. LPA receptors were expressed at significantly higher levels on Common Myeloid Progenitors (CMP) than either multipotent Hematopoietic Stem/Progenitor Cells (HSPC) or Common Lymphoid Progenitors (CLP) suggesting that LPA acts on committed myeloid progenitors. Functional studies demonstrated that LPA enhanced migration, induced cell proliferation and reduced apoptosis of isolated CMP, but had no effect on either HSPC or CLP. Analysis of adult and fetal human bone marrow sections showed that PPAP2A, (the enzyme which degrades LPA) was highly expressed in the osteoblastic niche but not in the perivascular regions, whereas Autotaxin (the enzyme that synthesizes LPA) was expressed in perivascular regions of the marrow. We propose that a gradient of LPA with the highest levels in peri-sinusoidal regions and lowest near the endosteal zone, regulates the localization, proliferation and differentiation of myeloid progenitors within the bone marrow marrow. Public Library of Science 2013-05-16 /pmc/articles/PMC3655943/ /pubmed/23696850 http://dx.doi.org/10.1371/journal.pone.0063718 Text en © 2013 Evseenko et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Evseenko, Denis
Latour, Brooke
Richardson, Wade
Corselli, Mirko
Sahaghian, Arineh
Cardinal, Sofie
Zhu, Yuhua
Chan, Rebecca
Dunn, Bruce
Crooks, Gay M.
Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment
title Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment
title_full Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment
title_fullStr Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment
title_full_unstemmed Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment
title_short Lysophosphatidic Acid Mediates Myeloid Differentiation within the Human Bone Marrow Microenvironment
title_sort lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655943/
https://www.ncbi.nlm.nih.gov/pubmed/23696850
http://dx.doi.org/10.1371/journal.pone.0063718
work_keys_str_mv AT evseenkodenis lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT latourbrooke lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT richardsonwade lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT corsellimirko lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT sahaghianarineh lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT cardinalsofie lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT zhuyuhua lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT chanrebecca lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT dunnbruce lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment
AT crooksgaym lysophosphatidicacidmediatesmyeloiddifferentiationwithinthehumanbonemarrowmicroenvironment