Authors
Michael R Hicks, Julia Hiserodt, Katrina Paras, Wakana Fujiwara, Ascia Eskin, Majib Jan, Haibin Xi, Courtney S Young, Denis Evseenko, Stanley F Nelson, Melissa J Spencer, Ben Van Handel, April D Pyle
Publication date
2018/1
Journal
Nature cell biology
Volume
20
Issue
1
Pages
46-57
Publisher
Nature Publishing Group UK
Description
Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenicity of hPSC-SMPCs relative to human fetal or adult satellite cells remains unclear. We observed that hPSC-SMPCs derived by directed differentiation are less functional in vitro and in vivo compared to human satellite cells. Using RNA sequencing, we found that the cell surface receptors ERBB3 and NGFR demarcate myogenic populations, including PAX7 progenitors in human fetal development and hPSC-SMPCs. We demonstrated that hPSC skeletal muscle is immature, but inhibition of transforming growth factor-β signalling during differentiation improved fusion efficiency, ultrastructural organization and the expression of adult myosins. This enrichment and maturation strategy restored dystrophin in hundreds of dystrophin-deficient myofibres after engraftment of CRISPR …
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