PUBLICATION

Transplantation-based screen identifies inducers of muscle progenitor cell engraftment across vertebrate species

Authors
Tavakoli, S., Garcia, V., Gähwiler, E., Adatto, I., Rangan, A., Messemer, K.A., Kakhki, S.A., Yang, S., Chan, V.S., Manning, M.E., Fotowat, H., Zhou, Y., Wagers, A.J., Zon, L.I.
ID
ZDB-PUB-230406-47
Date
2023
Source
Cell Reports   42: 112365112365 (Journal)
Registered Authors
Adatto, Isaac, Tavakoli, Sahar, Zhou, Yi, Zon, Leonard I.
Keywords
CP: Developmental biology, cell therapy, engraftment, lysophosphatidic acid, muscular dystrophy, niflumic acid, satellite cell
MeSH Terms
  • Animals
  • Cell Differentiation
  • Lipids/pharmacology
  • Mice
  • Muscle Development
  • Muscle, Skeletal/physiology
  • Satellite Cells, Skeletal Muscle*
  • Stem Cell Transplantation
  • Zebrafish*
PubMed
37018075 Full text @ Cell Rep.
Abstract
Stem cell transplantation presents a potentially curative strategy for genetic disorders of skeletal muscle, but this approach is limited by the deleterious effects of cell expansion in vitro and consequent poor engraftment efficiency. In an effort to overcome this limitation, we sought to identify molecular signals that enhance the myogenic activity of cultured muscle progenitors. Here, we report the development and application of a cross-species small-molecule screening platform employing zebrafish and mice, which enables rapid, direct evaluation of the effects of chemical compounds on the engraftment of transplanted muscle precursor cells. Using this system, we screened a library of bioactive lipids to discriminate those that could increase myogenic engraftment in vivo in zebrafish and mice. This effort identified two lipids, lysophosphatidic acid and niflumic acid, both linked to the activation of intracellular calcium-ion flux, which showed conserved, dose-dependent, and synergistic effects in promoting muscle engraftment across these vertebrate species.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping