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Establishment of stably expandable induced myogenic stem cells by four transcription factors

Title
Establishment of stably expandable induced myogenic stem cells by four transcription factors
Authors
Lee, Eun-JooKim, MinhyungKim, Yong DeukChung, Myung-JinElfadl, AhmedUlah, H. M. ArifPark, DongsuLee, SunrayPark, Hyun-SookKim, Tae-HwanHwang, DaeheeJeong, Kyu-Shik
DGIST Authors
Hwang, Daehee
Issue Date
2018-11
Citation
Cell Death and Disease, 9(11)
Type
Article
Article Type
Article
Keywords
SKELETAL-MUSCLE REGENERATIONSATELLITE CELLSPROGENITOR CELLSDIRECT CONVERSIONDEFINED FACTORSSELF-RENEWALMITOCHONDRIAL BIOGENESISFUNCTIONAL-NEURONSMOUSE FIBROBLASTSRECEPTOR-GAMMA
ISSN
2041-4889
Abstract
Life-long regeneration of healthy muscle by cell transplantation is an ideal therapy for patients with degenerative muscle diseases. Yet, obtaining muscle stem cells from patients is very limited due to their exhaustion in disease condition. Thus, development of a method to obtain healthy myogenic stem cells is required. Here, we showed that the four transcription factors, Six1, Eya1, Esrrb, and Pax3, converts fibroblasts into induced myogenic stem cells (iMSCs). The iMSCs showed effective differentiation into multinucleated myotubes and also higher proliferation capacity than muscle derived stem cells both in vitro and in vivo. The iMSCs do not lose their proliferation capacity though the passaging number is increased. We further isolated CD106-negative and α7-integrin-positive iMSCs (sort-iMSCs) showing higher myogenic differentiation capacity than iMSCs. Moreover, genome-wide transcriptomic analysis of iMSCs and sort-iMSCs, followed by network analysis, revealed the genes and signaling pathways associated with enhanced proliferation and differentiation capacity of iMSCs and sort-iMSCs, respectively. The stably expandable iMSCs provide a new source for drug screening and muscle regenerative therapy for muscle wasting disease. © 2018, The Author(s).
URI
http://hdl.handle.net/20.500.11750/9411
DOI
10.1038/s41419-018-1114-8
Publisher
Nature Publishing Group
Files:
There are no files associated with this item.
Collection:
Department of New BiologySystems Biology and Medicine Lab1. Journal Articles


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