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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics. / Davegårdh, Cajsa; Säll, Johanna; Benrick, Anna; Broholm, Christa; Volkov, Petr; Perfilyev, Alexander; Henriksen, Tora Ida; Wu, Yanling; Hjort, Line; Brøns, Charlotte; Hansson, Ola; Pedersen, Maria; Würthner, Jens U.; Pfeffer, Klaus; Nilsson, Emma; Vaag, Allan; Stener-Victorin, Elisabet; Pircs, Karolina; Scheele, Camilla; Ling, Charlotte.

In: Nature Communications, Vol. 12, No. 1, 2431, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Davegårdh, C, Säll, J, Benrick, A, Broholm, C, Volkov, P, Perfilyev, A, Henriksen, TI, Wu, Y, Hjort, L, Brøns, C, Hansson, O, Pedersen, M, Würthner, JU, Pfeffer, K, Nilsson, E, Vaag, A, Stener-Victorin, E, Pircs, K, Scheele, C & Ling, C 2021, 'VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics', Nature Communications, vol. 12, no. 1, 2431. https://doi.org/10.1038/s41467-021-22068-5

APA

Davegårdh, C., Säll, J., Benrick, A., Broholm, C., Volkov, P., Perfilyev, A., Henriksen, T. I., Wu, Y., Hjort, L., Brøns, C., Hansson, O., Pedersen, M., Würthner, J. U., Pfeffer, K., Nilsson, E., Vaag, A., Stener-Victorin, E., Pircs, K., Scheele, C., & Ling, C. (2021). VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics. Nature Communications, 12(1), [2431]. https://doi.org/10.1038/s41467-021-22068-5

Vancouver

Davegårdh C, Säll J, Benrick A, Broholm C, Volkov P, Perfilyev A et al. VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics. Nature Communications. 2021;12(1). 2431. https://doi.org/10.1038/s41467-021-22068-5

Author

Davegårdh, Cajsa ; Säll, Johanna ; Benrick, Anna ; Broholm, Christa ; Volkov, Petr ; Perfilyev, Alexander ; Henriksen, Tora Ida ; Wu, Yanling ; Hjort, Line ; Brøns, Charlotte ; Hansson, Ola ; Pedersen, Maria ; Würthner, Jens U. ; Pfeffer, Klaus ; Nilsson, Emma ; Vaag, Allan ; Stener-Victorin, Elisabet ; Pircs, Karolina ; Scheele, Camilla ; Ling, Charlotte. / VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics. In: Nature Communications. 2021 ; Vol. 12, No. 1.

Bibtex

@article{fe7203d4bb484fb9bc17158a4dcfb154,
title = "VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics",
abstract = "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.",
author = "Cajsa Daveg{\aa}rdh and Johanna S{\"a}ll and Anna Benrick and Christa Broholm and Petr Volkov and Alexander Perfilyev and Henriksen, {Tora Ida} and Yanling Wu and Line Hjort and Charlotte Br{\o}ns and Ola Hansson and Maria Pedersen and W{\"u}rthner, {Jens U.} and Klaus Pfeffer and Emma Nilsson and Allan Vaag and Elisabet Stener-Victorin and Karolina Pircs and Camilla Scheele and Charlotte Ling",
note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
doi = "10.1038/s41467-021-22068-5",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics

AU - Davegårdh, Cajsa

AU - Säll, Johanna

AU - Benrick, Anna

AU - Broholm, Christa

AU - Volkov, Petr

AU - Perfilyev, Alexander

AU - Henriksen, Tora Ida

AU - Wu, Yanling

AU - Hjort, Line

AU - Brøns, Charlotte

AU - Hansson, Ola

AU - Pedersen, Maria

AU - Würthner, Jens U.

AU - Pfeffer, Klaus

AU - Nilsson, Emma

AU - Vaag, Allan

AU - Stener-Victorin, Elisabet

AU - Pircs, Karolina

AU - Scheele, Camilla

AU - Ling, Charlotte

N1 - Publisher Copyright: © 2021, The Author(s).

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-22068-5

DO - 10.1038/s41467-021-22068-5

M3 - Journal article

C2 - 33893273

AN - SCOPUS:85104824362

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2431

ER -

ID: 272421903