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

Publication date: 27 June 2017
Source:Cell Reports, Volume 19, Issue 13
Author(s): 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
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.

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Teaser

Magli et al. investigate the transcriptional changes that occur during PAX7-mediated myogenic commitment from human pluripotent stem cells and identify CD54, integrin α9β1, and SDC2 as surface markers that enable the purification of myogenic progenitors endowed with long-term regenerative potential.


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