Stem Cell-Associated Proteins and Extracellular Matrix Composition of the Human Atrioventricular Junction

The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a potential stem cell niche region. Little is known about the protein composition of the human AVj. To map the extracellular matrix (ECM) and...

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Published inCells (Basel, Switzerland) Vol. 13; no. 24; p. 2048
Main Authors Thorsell, Annika, Sjölin, Linnéa, Berger, Evelin, Jeppsson, Anders, Oldfors, Anders, Rotter Sopasakis, Victoria, Vukusic, Kristina
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.12.2024
MDPI
Subjects
Adult
Aged
atrioventricular junction
Biomarkers
Biomarkers - metabolism
Biopsy
Blood & organ donations
cardiac regeneration
Cardiomyocytes
Cell Biology
Cell Differentiation
Cellbiologi
Chromatography
Extracellular matrix
Extracellular Matrix - metabolism
Female
Gene expression
Genes
global quantitative proteomics
Heart
Heart Ventricles - cytology
Heart Ventricles - metabolism
Histology
Humans
Hypoxia
Immunohistochemistry
Invoices
Male
Microenvironments
Middle Aged
mRNA-seq
Particle size
Peptides
Protein composition
Proteins
Proteomics
Proteomics - methods
RNA
RNA sequencing
Signal transduction
stem cell niche
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Transforming growth factor-b
Transforming growth factors
Wnt protein
United States
Sweden
Massachusetts
United States > US
cardiomyocytes
cardiac regeneration
global quantitative proteomics
stem cell niche
mRNA-seq
atrioventricular junction
extracellular matrix
heart
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Abstract The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a potential stem cell niche region. Little is known about the protein composition of the human AVj. To map the extracellular matrix (ECM) and expression of stem cell-related biomarkers, this study compares protein and gene expression patterns in AVj and Left Ventricular (LV) tissues. Biopsies were collected from 15 human hearts. Global quantitative proteomics and mRNA sequencing were used to identify differentially expressed proteins and altered genes. Of the total 4904 identified proteins, 1138 were differently expressed between the AVj and LV. While the top proteins in LV were involved in cardiac motor function and energy regulation, the AVj displayed proteins associated with early cardiomyocyte development, differentiation, proliferation, migration, and hypoxia. Furthermore, several developmental signalling pathways, including TGF-β, TNF, WNT, Notch, and FGF, were represented. RNA-seq data verified that the expressed genes were involved with differentiation, cell growth, proliferation, or ECM organization. Immunohistochemistry confirmed the expression of the stem cell-related biomarkers NPPA and POSTN in the AVj, further strengthening the hypothesis of the AVj as a specialized microenvironment conducive to stem cell niche activity.
AbstractList The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a potential stem cell niche region. Little is known about the protein composition of the human AVj. To map the extracellular matrix (ECM) and expression of stem cell-related biomarkers, this study compares protein and gene expression patterns in AVj and Left Ventricular (LV) tissues. Biopsies were collected from 15 human hearts. Global quantitative proteomics and mRNA sequencing were used to identify differentially expressed proteins and altered genes. Of the total 4904 identified proteins, 1138 were differently expressed between the AVj and LV. While the top proteins in LV were involved in cardiac motor function and energy regulation, the AVj displayed proteins associated with early cardiomyocyte development, differentiation, proliferation, migration, and hypoxia. Furthermore, several developmental signalling pathways, including TGF-β, TNF, WNT, Notch, and FGF, were represented. RNA-seq data verified that the expressed genes were involved with differentiation, cell growth, proliferation, or ECM organization. Immunohistochemistry confirmed the expression of the stem cell-related biomarkers NPPA and POSTN in the AVj, further strengthening the hypothesis of the AVj as a specialized microenvironment conducive to stem cell niche activity.
The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a potential stem cell niche region. Little is known about the protein composition of the human AVj. To map the extracellular matrix (ECM) and expression of stem cell-related biomarkers, this study compares protein and gene expression patterns in AVj and Left Ventricular (LV) tissues. Biopsies were collected from 15 human hearts. Global quantitative proteomics and mRNA sequencing were used to identify differentially expressed proteins and altered genes. Of the total 4904 identified proteins, 1138 were differently expressed between the AVj and LV. While the top proteins in LV were involved in cardiac motor function and energy regulation, the AVj displayed proteins associated with early cardiomyocyte development, differentiation, proliferation, migration, and hypoxia. Furthermore, several developmental signalling pathways, including TGF-β, TNF, WNT, Notch, and FGF, were represented. RNA-seq data verified that the expressed genes were involved with differentiation, cell growth, proliferation, or ECM organization. Immunohistochemistry confirmed the expression of the stem cell-related biomarkers NPPA and POSTN in the AVj, further strengthening the hypothesis of the AVj as a specialized microenvironment conducive to stem cell niche activity.The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a potential stem cell niche region. Little is known about the protein composition of the human AVj. To map the extracellular matrix (ECM) and expression of stem cell-related biomarkers, this study compares protein and gene expression patterns in AVj and Left Ventricular (LV) tissues. Biopsies were collected from 15 human hearts. Global quantitative proteomics and mRNA sequencing were used to identify differentially expressed proteins and altered genes. Of the total 4904 identified proteins, 1138 were differently expressed between the AVj and LV. While the top proteins in LV were involved in cardiac motor function and energy regulation, the AVj displayed proteins associated with early cardiomyocyte development, differentiation, proliferation, migration, and hypoxia. Furthermore, several developmental signalling pathways, including TGF-β, TNF, WNT, Notch, and FGF, were represented. RNA-seq data verified that the expressed genes were involved with differentiation, cell growth, proliferation, or ECM organization. Immunohistochemistry confirmed the expression of the stem cell-related biomarkers NPPA and POSTN in the AVj, further strengthening the hypothesis of the AVj as a specialized microenvironment conducive to stem cell niche activity.
The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a potential stem cell niche region. Little is known about the protein composition of the human AVj. To map the extracellular matrix (ECM) and expression of stem cell-related biomarkers, this study compares protein and gene expression patterns in AVj and Left Ventricular (LV) tissues. Biopsies were collected from 15 human hearts. Global quantitative proteomics and mRNA sequencing were used to identify differentially expressed proteins and altered genes. Of the total 4904 identified proteins, 1138 were differently expressed between the AVj and LV. While the top proteins in LV were involved in cardiac motor function and energy regulation, the AVj displayed proteins associated with early cardiomyocyte development, differentiation, proliferation, migration, and hypoxia. Furthermore, several developmental signalling pathways, including TGF-beta, TNF, WNT, Notch, and FGF, were represented. RNA-seq data verified that the expressed genes were involved with differentiation, cell growth, proliferation, or ECM organization. Immunohistochemistry confirmed the expression of the stem cell-related biomarkers NPPA and POSTN in the AVj, further strengthening the hypothesis of the AVj as a specialized microenvironment conducive to stem cell niche activity.
Audience Academic
Author Thorsell, Annika
Oldfors, Anders
Vukusic, Kristina
Sjölin, Linnéa
Berger, Evelin
Rotter Sopasakis, Victoria
Jeppsson, Anders
AuthorAffiliation 6 Region Västra Götaland, Department of Clinical Chemistry, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
5 Department of Pathology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
4 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
1 Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
2 Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden
3 Region Västra Götaland, Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
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– name: 3 Region Västra Götaland, Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
– name: 5 Department of Pathology, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
– name: 2 Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden
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Issue 24
Keywords cardiomyocytes
cardiac regeneration
global quantitative proteomics
stem cell niche
mRNA-seq
atrioventricular junction
extracellular matrix
heart
Language English
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These authors contributed equally to this work.
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Snippet The human heart regenerates slowly through life, but how new cells are generated is mostly unknown. The atrioventricular junction (AVj) has been indicated as a...
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StartPage 2048
SubjectTerms Adult
Aged
atrioventricular junction
Biomarkers
Biomarkers - metabolism
Biopsy
Blood & organ donations
cardiac regeneration
Cardiomyocytes
Cell Biology
Cell Differentiation
Cellbiologi
Chromatography
Extracellular matrix
Extracellular Matrix - metabolism
Female
Gene expression
Genes
global quantitative proteomics
Heart
Heart Ventricles - cytology
Heart Ventricles - metabolism
Histology
Humans
Hypoxia
Immunohistochemistry
Invoices
Male
Microenvironments
Middle Aged
mRNA-seq
Particle size
Peptides
Protein composition
Proteins
Proteomics
Proteomics - methods
RNA
RNA sequencing
Signal transduction
stem cell niche
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Transforming growth factor-b
Transforming growth factors
Wnt protein
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Title Stem Cell-Associated Proteins and Extracellular Matrix Composition of the Human Atrioventricular Junction
URI https://www.ncbi.nlm.nih.gov/pubmed/39768140
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https://pubmed.ncbi.nlm.nih.gov/PMC11674807
https://gup.ub.gu.se/publication/345593
https://doaj.org/article/a0be63df587241019beed1f895dc3f40
Volume 13
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