dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors

Basem M. Abdallah, Patrice Boissy, Qihua Tan, Jesper Dahlgaard, Gunnhildur A Traustadottir, Katarzyna Kupisiewicz, Jorge Laborda, Jean-Marie Delaisse, Moustapha Kassem

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

 
Udgivelsesdato: 2007-Mar-9
OriginalsprogEngelsk
TidsskriftJournal of Biological Chemistry
Vol/bind282
Udgave nummer10
Sider (fra-til)7339-7351
Antal sider12
ISSN0021-9258
DOI
StatusUdgivet - 9. mar. 2007

Fingeraftryk

Stem cells
Mesenchymal Stromal Cells
Gene expression
Bone
Cytokines
Antigens
Homeodomain Proteins
NF-kappa B
Osteoblasts
Cell adhesion
Cell proliferation
Microarrays
Epidermal Growth Factor
Adipocytes
Cell Adhesion
Endotoxins
Transcriptional Activation
Lipopolysaccharides
Genes
Cell Proliferation

Citer dette

@article{8e277ed0cb1f11dc8674000ea68e967b,
title = "dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors",
abstract = "dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24{\%} of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-kappaB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment {"}niche.{"} Our findings also demonstrate a role for Dlk1 in mediating the immune response.",
keywords = "Adipocytes, B-Lymphocytes, Bone Marrow Cells, Cell Differentiation, Cytokines, Gene Expression Regulation, Humans, Intercellular Signaling Peptides and Proteins, Lymphocyte Activation, Membrane Proteins, Mesenchymal Stem Cells, NF-kappa B, Oligonucleotide Array Sequence Analysis, Osteoblasts",
author = "Abdallah, {Basem M.} and Patrice Boissy and Qihua Tan and Jesper Dahlgaard and Traustadottir, {Gunnhildur A} and Katarzyna Kupisiewicz and Jorge Laborda and Jean-Marie Delaisse and Moustapha Kassem",
year = "2007",
month = "3",
day = "9",
doi = "10.1074/jbc.M607530200",
language = "English",
volume = "282",
pages = "7339--7351",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "10",

}

dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors. / Abdallah, Basem M.; Boissy, Patrice; Tan, Qihua; Dahlgaard, Jesper; Traustadottir, Gunnhildur A; Kupisiewicz, Katarzyna; Laborda, Jorge; Delaisse, Jean-Marie; Kassem, Moustapha.

I: Journal of Biological Chemistry, Bind 282, Nr. 10, 09.03.2007, s. 7339-7351.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors

AU - Abdallah, Basem M.

AU - Boissy, Patrice

AU - Tan, Qihua

AU - Dahlgaard, Jesper

AU - Traustadottir, Gunnhildur A

AU - Kupisiewicz, Katarzyna

AU - Laborda, Jorge

AU - Delaisse, Jean-Marie

AU - Kassem, Moustapha

PY - 2007/3/9

Y1 - 2007/3/9

N2 - dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-kappaB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment "niche." Our findings also demonstrate a role for Dlk1 in mediating the immune response.

AB - dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-kappaB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment "niche." Our findings also demonstrate a role for Dlk1 in mediating the immune response.

KW - Adipocytes

KW - B-Lymphocytes

KW - Bone Marrow Cells

KW - Cell Differentiation

KW - Cytokines

KW - Gene Expression Regulation

KW - Humans

KW - Intercellular Signaling Peptides and Proteins

KW - Lymphocyte Activation

KW - Membrane Proteins

KW - Mesenchymal Stem Cells

KW - NF-kappa B

KW - Oligonucleotide Array Sequence Analysis

KW - Osteoblasts

U2 - 10.1074/jbc.M607530200

DO - 10.1074/jbc.M607530200

M3 - Journal article

C2 - 17182623

VL - 282

SP - 7339

EP - 7351

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 10

ER -