Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors

Abstract Background Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell–cell and cell–matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic maligna...

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Main Authors: Francesco Da Ros, Luca Persano, Dario Bizzotto, Mariagrazia Michieli, Paola Braghetta, Mario Mazzucato, Paolo Bonaldo
Format: Article
Language:English
Published: BMC 2022-01-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-021-02674-2
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author Francesco Da Ros
Luca Persano
Dario Bizzotto
Mariagrazia Michieli
Paola Braghetta
Mario Mazzucato
Paolo Bonaldo
author_facet Francesco Da Ros
Luca Persano
Dario Bizzotto
Mariagrazia Michieli
Paola Braghetta
Mario Mazzucato
Paolo Bonaldo
author_sort Francesco Da Ros
collection DOAJ
description Abstract Background Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell–cell and cell–matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic malignancies. Here we describe Emilin-2 as an abundant extracellular matrix component of bone marrow stroma. Methods Immunodetection of Emilin-2 was performed in bone marrow sections of mice from 30 days to 6 months of age. Emilin-2 expression was monitored in vitro in primary and mesenchymal stem cell lines under undifferentiated and adipogenic conditions. Hematopoietic stem cells and progenitors in bone marrow of 3- to 10-month-old wild-type and Emilin-2 null mice were analyzed by flow cytometry. Results Emilin-2 is deposited in bone marrow extracellular matrix in an age-dependent manner, forming a meshwork that extends from compact bone boundaries to the central trabecular regions. Emilin-2 is expressed and secreted by both primary and immortalized bone marrow mesenchymal stem cells, exerting an inhibitory action in adipogenic differentiation. In vivo Emilin-2 deficiency impairs the frequency of hematopoietic stem/progenitor cells in bone marrow during aging. Conclusion Our data provide new insights in the contribution of bone marrow extracellular matrix microenvironment in the regulation of stem cell niches and hematopoietic progenitor differentiation.
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spelling doaj.art-62978c7a11514636aed905ec1b58ee462022-12-22T04:09:25ZengBMCStem Cell Research & Therapy1757-65122022-01-0113111510.1186/s13287-021-02674-2Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitorsFrancesco Da Ros0Luca Persano1Dario Bizzotto2Mariagrazia Michieli3Paola Braghetta4Mario Mazzucato5Paolo Bonaldo6SOSd Cell Stem Unit, Department of Translational Research, National Cancer Center CRO-IRCSSDepartment of Women’s and Children’s Health, University of PadovaDepartment of Molecular Medicine, University of PadovaSOSd Cell Therapy and High Dose Chemotherapy, National Cancer Center CRO- IRCCSDepartment of Molecular Medicine, University of PadovaSOSd Cell Stem Unit, Department of Translational Research, National Cancer Center CRO-IRCSSDepartment of Molecular Medicine, University of PadovaAbstract Background Dissection of mechanisms involved in the regulation of bone marrow microenvironment through cell–cell and cell–matrix contacts is essential for the detailed understanding of processes underlying bone marrow activities both under physiological conditions and in hematologic malignancies. Here we describe Emilin-2 as an abundant extracellular matrix component of bone marrow stroma. Methods Immunodetection of Emilin-2 was performed in bone marrow sections of mice from 30 days to 6 months of age. Emilin-2 expression was monitored in vitro in primary and mesenchymal stem cell lines under undifferentiated and adipogenic conditions. Hematopoietic stem cells and progenitors in bone marrow of 3- to 10-month-old wild-type and Emilin-2 null mice were analyzed by flow cytometry. Results Emilin-2 is deposited in bone marrow extracellular matrix in an age-dependent manner, forming a meshwork that extends from compact bone boundaries to the central trabecular regions. Emilin-2 is expressed and secreted by both primary and immortalized bone marrow mesenchymal stem cells, exerting an inhibitory action in adipogenic differentiation. In vivo Emilin-2 deficiency impairs the frequency of hematopoietic stem/progenitor cells in bone marrow during aging. Conclusion Our data provide new insights in the contribution of bone marrow extracellular matrix microenvironment in the regulation of stem cell niches and hematopoietic progenitor differentiation.https://doi.org/10.1186/s13287-021-02674-2Extracellular matrixBone marrowMesenchymal stem cellsEmilin-2
spellingShingle Francesco Da Ros
Luca Persano
Dario Bizzotto
Mariagrazia Michieli
Paola Braghetta
Mario Mazzucato
Paolo Bonaldo
Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
Stem Cell Research & Therapy
Extracellular matrix
Bone marrow
Mesenchymal stem cells
Emilin-2
title Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
title_full Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
title_fullStr Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
title_full_unstemmed Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
title_short Emilin-2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
title_sort emilin 2 is a component of bone marrow extracellular matrix regulating mesenchymal stem cell differentiation and hematopoietic progenitors
topic Extracellular matrix
Bone marrow
Mesenchymal stem cells
Emilin-2
url https://doi.org/10.1186/s13287-021-02674-2
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