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

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

doi:10.1016/j.celrep.2017.06.005

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

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

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56 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2867-2877
Number of pages	11
Journal	Cell reports
Volume	19
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2017.06.005
State	Published - Jun 27 2017

Bibliographical note

Funding Information:
This project was supported by NIH grants R01 AR055299 (to R.C.R.P.) and U01 HL100407R01 (to R.C.R.P. and J.A.T.), the Greg Marzolf Jr. Foundation (to R.C.R.P.), ADVault, Inc. and MyDirectives.com (to R.C.R.P.), and by Regenerative Medicine Minnesota MRM 2015 PDSCH 003 (to A.M.). The cytogenetic analyses were performed in the Cytogenomics Shared Resource at the University of Minnesota, with support from the comprehensive Masonic Cancer Center NIH grant #P30 CA077598-09. The authors thank Dr. Jaemin Kim for his assistance with the serum-free differentiation protocol and Dr. Nelio Oliveira for his assistance with the teratoma experiments.

Publisher Copyright:
© 2017 The Author(s)

Keywords

CD54
ChIP sequencing
PAX7
RNA sequencing
SDC2
integrin α9β1
muscle regeneration
muscular dystrophy
skeletal myogenesis
stem cell therapy

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10.1016/j.celrep.2017.06.005

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528177

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Magli, A., Incitti, T., Kiley, J., Swanson, S. A., Darabi, R., Rinaldi, F., Selvaraj, S., Yamamoto, A., Tolar, J., Yuan, C., Stewart, R., Thomson, J. A., & Perlingeiro, R. C. R. (2017). PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors. Cell reports, 19(13), 2867-2877. https://doi.org/10.1016/j.celrep.2017.06.005

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abstract = "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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AU - Kiley, James

AU - Swanson, Scott A.

AU - Darabi, Radbod

AU - Rinaldi, Fabrizio

AU - Selvaraj, Sridhar

AU - Yamamoto, Ami

AU - Tolar, Jakub

AU - Yuan, Ce

AU - Stewart, Ron

AU - Thomson, James A.

AU - Perlingeiro, Rita C.R.

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N2 - 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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PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors

Abstract

Bibliographical note

Keywords

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