VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics.

Animals Autophagy / genetics Autophagy-Related Proteins / deficiency Cell Differentiation / genetics Cells, Cultured Diabetes Mellitus, Type 2 / genetics Epigenesis, Genetic / genetics Epigenomics / methods Female Gene Expression Profiling / methods Humans Male Mice, Inbred C57BL Mice, Knockout Middle Aged Muscle Development / genetics Myoblasts / metabolism Stem Cells / metabolism Vesicular Transport Proteins / deficiency

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
23 04 2021
Historique:
received: 16 08 2019
accepted: 25 02 2021
entrez: 24 4 2021
pubmed: 25 4 2021
medline: 11 5 2021
Statut: epublish

Résumé

Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39

Identifiants

DOI: 10.1038/s41467-021-22068-5 PMID: 33893273 PMC: PMC8065135
pubmed: 33893273
doi: 10.1038/s41467-021-22068-5
pii: 10.1038/s41467-021-22068-5
pmc: PMC8065135
doi:

Substances chimiques

Autophagy-Related Proteins 0
VPS39 protein, human 0
Vesicular Transport Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2431

Commentaires et corrections

Type : CommentIn

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Auteurs

Cajsa Davegårdh (C)

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
ORCID: 0000-0003-1124-7570

Johanna Säll (J)

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
ORCID: 0000-0001-7337-4140

Anna Benrick (A)

Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
School of Health Sciences, University of Skövde, Skövde, Sweden.

Christa Broholm (C)

Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.

Petr Volkov (P)

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.

Alexander Perfilyev (A)

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.
ORCID: 0000-0003-1136-8946

Tora Ida Henriksen (TI)

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Yanling Wu (Y)

Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Line Hjort (L)

Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.

Charlotte Brøns (C)

Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.

Ola Hansson (O)

Genomics, Diabetes and Endocrinology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.
ORCID: 0000-0002-7394-7639

Maria Pedersen (M)

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Jens U Würthner (JU)

ADC Therapeutics, Biopole, Epalinges, Switzerland.

Klaus Pfeffer (K)

Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

Emma Nilsson (E)

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden.

Allan Vaag (A)

Steno Diabetes Center Copenhagen, Gentofte, Denmark.

Elisabet Stener-Victorin (E)

Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
ORCID: 0000-0002-3424-1502

Karolina Pircs (K)

Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Lund, Sweden.

Camilla Scheele (C)

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Charlotte Ling (C)

Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden. charlotte.ling@med.lu.se.
ORCID: 0000-0003-0587-7154

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Autophagie › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à l'autophagie › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Cellules › Cellules cultivées › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Épigénomique › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système locomoteur › Développement locomoteur › Développement musculaire › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Cellules › Cellules souches › Myoblastes › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Cellules › Cellules souches › VPS39-deficiency observed in type 2 diabetes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines du transport vésiculaire › VPS39-deficiency observed in type 2 diabetes...