PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors

• Main Authors: Alessandro Magli, Tania Incitti, James Kiley, Scott A. Swanson, Radbod Darabi, Fabrizio Rinaldi, Sridhar Selvaraj, Ami Yamamoto, Jakub Tolar, Ce Yuan, Ron Stewart, James A. Thomson, Rita C.R. Perlingeiro
• Format: Article
• Language: English
• Published: Elsevier 2017-06-01
• Series: Cell Reports
• Subjects: stem cell therapy; skeletal myogenesis; muscular dystrophy; RNA sequencing; muscle regeneration; ChIP sequencing; PAX7; CD54; integrin α9β1; SDC2
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717307830

Pluripotent stem (PS)-cell-derived cell types hold promise for treating degenerative diseases. However, PS cell differentiation is intrinsically heterogeneous; therefore, clinical translation requires the development of practical methods for isolating progenitors from unwanted and potentially teratogenic cells. Muscle-regenerating progenitors can be derived through transient PAX7 expression. To better understand the biology, and to discover potential markers for these cells, here we investigate PAX7 genomic targets and transcriptional changes in human cells undergoing PAX7-mediated myogenic commitment. We identify CD54, integrin α9β1, and Syndecan2 (SDC2) as surface markers on PAX7-induced myogenic progenitors. We show that these markers allow for the isolation of myogenic progenitors using both fluorescent- and CGMP-compatible magnetic-based sorting technologies and that CD54+α9β1+SDC2+ cells contribute to long-term muscle regeneration in vivo. These findings represent a critical step toward enabling the translation of PS-cell-based therapies for muscle diseases.