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

Autor: Sahar Tavakoli, Vivian Garcia, Eric Gähwiler, Isaac Adatto, Apoorva Rangan, Kathleen A. Messemer, Sara Ashrafi Kakhki, Song Yang, Victoria S. Chan, Margot E. Manning, Haleh Fotowat, Yi Zhou, Amy J. Wagers, Leonard I. Zon
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 4, Pp 112365- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112365
Popis: Summary: 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.
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