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VPS39-deficiency ob...
VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics
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- Davegårdh, Cajsa (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden
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- Säll, Johanna (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden
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- Benrick, Anna, 1979 (author)
- Högskolan i Skövde,University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Translationell medicin TRIM, Translational Medicine
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- Broholm, C. (author)
- Copenhagen University Hospital,Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
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- Volkov, Petr (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden
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- Perfilyev, Alexander (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden
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- Henriksen, T. I. (author)
- The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark
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- Wu, Yanling, 1985 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden
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- Hjort, Line (author)
- Copenhagen University Hospital,Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark ; Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark
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- Brons, C. (author)
- Copenhagen University Hospital,Diabetes and Bone-metabolic Research Unit, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
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- Hansson, Ola (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Institute for Molecular Medicine Finland (FIMM),Genomics, Diabetes and Endocrinology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden ; Finnish Institute of Molecular Medicine, University of Helsinki, Finland
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- Pedersen, M. (author)
- The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark
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- Wurthner, J. U. (author)
- ADC Therapeutics, Biopole, Epalinges, Switzerland
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- Pfeffer, K. (author)
- Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Germany
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- Nilsson, Emma (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden
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- Vaag, Allan (author)
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
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- Stener-Victorin, E. (author)
- Karolinska Institutet,Karolinska Institute,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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- Pircs, Karolina (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Wallenberg Neurocentrum, Lund,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Wallenberg Neuroscience Centre, Lund,Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, Sweden
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- Scheele, C. (author)
- The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark ; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
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- Ling, Charlotte (author)
- Lund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Scania University Hospital, Malmö, Sweden
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(creator_code:org_t)
- 2021-04-23
- 2021
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Abstract
Subject headings
Close
- 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(+/-) mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- messenger-rna expression
- wide DNA methylation
- open-access database
- skeletal-muscle
- gene-expression
- satellite cells
- adipose-tissue
- regeneration
- protein
- transcription
- Science & Technology - Other Topics
- Translationell medicin TRIM
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Davegårdh, Cajsa
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Säll, Johanna
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Benrick, Anna, 1 ...
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Broholm, C.
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Volkov, Petr
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Perfilyev, Alexa ...
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show more...
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Henriksen, T. I.
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Wu, Yanling, 198 ...
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Hjort, Line
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Brons, C.
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Hansson, Ola
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Pedersen, M.
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Wurthner, J. U.
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Pfeffer, K.
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Nilsson, Emma
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Vaag, Allan
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Stener-Victorin, ...
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Pircs, Karolina
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Scheele, C.
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Ling, Charlotte
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Neurology
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MEDICAL AND HEAL ...
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and Endocrinology an ...
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Nature Communica ...
- By the university
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University of Gothenburg
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Lund University
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Karolinska Institutet
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University of Skövde