PXD043200-1

PXD043200 is an original dataset announced via ProteomeXchange.

Title	Engineering of human myotubes towards a mature metabolic and contractile phenotype
Description	Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current skeletal-muscle-models in vitro are incapable of fully recapitulating its physiological functions especially regarding exercise. Supplementation of IGF1, a growth factor secreted by myofibers in vivo, might help to overcome these limitations. Primary human CD56-positive myoblasts were differentiated into myotubes in the presence/absence of IGF1 in serum-free medium for 10 days. Daily collected samples were analyzed by proteomics, qRT-PCR and myotube contractibility via electrical-pulse-stimulation (EPS). Mitochondrial respiration and glucose uptake were measured. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon EPS following day 6 while myotubes without IGF1 were almost incapable of contraction. IGF1-treatment upregulated particularly muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. Elevated PPARGC1A, MYH7 and reduced MYH1/2 suggest a switch towards a more oxidative phenotype in line with elevated mitochondrial respiration. IGF1-treatment also upregulated expression of GLUT4 and increased insulin-dependent glucose uptake. To conclude, utilizing IGF1, we engineered human myotubes that recapitulate the physiological traits of skeletal muscle in vivo vastly superior to established protocols. This novel model enables investigation of exercise on a molecular level, drug screening and interorgan-crosstalk by transfer to organ-on-chip.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_05:07:53.941.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christine von Toerne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-22 03:02:15	ID requested
⏵ 1	2024-10-17 05:07:54	announced

10.1152/ajpcell.00654.2023;

Dreher SI, Grubba P, von Toerne C, Moruzzi A, Maurer J, Goj T, Birkenfeld AL, Peter A, Loskill P, Hauck SM, Weigert C, IGF1 promotes human myotube differentiation toward a mature metabolic and contractile phenotype. Am J Physiol Cell Physiol, 326(5):C1462-C1481(2024) [pubmed]

submitter keyword: Myotubes, mass spectrometry, IGF, immunohistochemistry

Cora Weigert
contact affiliation	Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany
contact email	cora.weigert@med.uni-tuebingen.de
lab head
Christine von Toerne
contact affiliation	Helmholtz Zentrum München
contact email	vontoerne@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043200
     1. Label: PRIDE project
     2. Name: Engineering of human myotubes towards a mature metabolic and contractile phenotype