Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.

<h4>Rationale</h4>Hematopoietic stem/progenitor cells (HSPC) are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may...

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Autores principales:	Yingmei Feng, Sarah Schouteden, Rachel Geenens, Vik Van Duppen, Paul Herijgers, Paul Holvoet, Paul P Van Veldhoven, Catherine M Verfaillie
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b2fcfb1efc154ad09a2d8cf1865d6154
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spelling	oai:doaj.org-article:b2fcfb1efc154ad09a2d8cf1865d61542021-11-18T08:09:50ZHematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.1932-620310.1371/journal.pone.0047286https://doaj.org/article/b2fcfb1efc154ad09a2d8cf1865d61542012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144813/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Rationale</h4>Hematopoietic stem/progenitor cells (HSPC) are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may increase HSPC proliferation and differentiation.<h4>Objectives</h4>We hypothesized that LDL may enhance HSPC proliferation and differentiation while HDL might have the opposing effect which might influence the size of the pool of inflammatory cells.<h4>Methods and results</h4>HSPC number and function were studied in hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice on high fat diet. Hypercholesterolemia was associated with increased frequency of HSPC, monocytes and granulocytes in the peripheral blood (PB). In addition, an increased proportion of BM HSPC was in G(2)M of the cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors (GMP) increased in BM of LDLr(-/-) mice. When BM Lin-Sca-1+cKit+ (i.e. "LSK") cells were cultured in the presence of LDL in vitro we also found enhanced differentiation towards monocytes and granulocytes. Furthermore, LDL promoted lineage negative (Lin-) cells motility. The modulation by LDL on HSPC differentiation into granulocytes and motility was inhibited by inhibiting ERK phosphorylation. By contrast, when mice were infused with human apoA-I (the major apolipoprotein of HDL) or reconstituted HDL (rHDL), the frequency and proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL-induced monocyte and granulocyte differentiation in vitro.<h4>Conclusion</h4>Our data suggest that LDL and HDL have opposing effects on HSPC proliferation and differentiation. It will be of interest to determine if breakdown of HSPC homeostasis by hypercholesterolemia contributes to inflammation and atherosclerosis progression.Yingmei FengSarah SchoutedenRachel GeenensVik Van DuppenPaul HerijgersPaul HolvoetPaul P Van VeldhovenCatherine M VerfailliePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e47286 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yingmei Feng Sarah Schouteden Rachel Geenens Vik Van Duppen Paul Herijgers Paul Holvoet Paul P Van Veldhoven Catherine M Verfaillie Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
description	<h4>Rationale</h4>Hematopoietic stem/progenitor cells (HSPC) are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may increase HSPC proliferation and differentiation.<h4>Objectives</h4>We hypothesized that LDL may enhance HSPC proliferation and differentiation while HDL might have the opposing effect which might influence the size of the pool of inflammatory cells.<h4>Methods and results</h4>HSPC number and function were studied in hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice on high fat diet. Hypercholesterolemia was associated with increased frequency of HSPC, monocytes and granulocytes in the peripheral blood (PB). In addition, an increased proportion of BM HSPC was in G(2)M of the cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors (GMP) increased in BM of LDLr(-/-) mice. When BM Lin-Sca-1+cKit+ (i.e. "LSK") cells were cultured in the presence of LDL in vitro we also found enhanced differentiation towards monocytes and granulocytes. Furthermore, LDL promoted lineage negative (Lin-) cells motility. The modulation by LDL on HSPC differentiation into granulocytes and motility was inhibited by inhibiting ERK phosphorylation. By contrast, when mice were infused with human apoA-I (the major apolipoprotein of HDL) or reconstituted HDL (rHDL), the frequency and proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL-induced monocyte and granulocyte differentiation in vitro.<h4>Conclusion</h4>Our data suggest that LDL and HDL have opposing effects on HSPC proliferation and differentiation. It will be of interest to determine if breakdown of HSPC homeostasis by hypercholesterolemia contributes to inflammation and atherosclerosis progression.
format	article
author	Yingmei Feng Sarah Schouteden Rachel Geenens Vik Van Duppen Paul Herijgers Paul Holvoet Paul P Van Veldhoven Catherine M Verfaillie
author_facet	Yingmei Feng Sarah Schouteden Rachel Geenens Vik Van Duppen Paul Herijgers Paul Holvoet Paul P Van Veldhoven Catherine M Verfaillie
author_sort	Yingmei Feng
title	Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
title_short	Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
title_full	Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
title_fullStr	Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
title_full_unstemmed	Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
title_sort	hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/b2fcfb1efc154ad09a2d8cf1865d6154
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Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.

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