Effect of Notch1 signaling on muscle engraftment and maturation from pluripotent stem cells

Notch1 信号对多能干细胞肌肉植入和成熟的影响

阅读:3
作者:Aline M S Yamashita, Bayardo I Garay, Hyunkee Kim, Darko Bosnakovski, Juan E Abrahante, Karim Azzag, Phablo Abreu, Aaron Ahlquist, Rita C R Perlingeiro

Abstract

Pax3-induced pluripotent stem cell-derived myogenic progenitors display an embryonic molecular signature but become postnatal upon transplantation. Because this correlates with upregulation of Notch signaling, here we probed whether NOTCH1 is required for in vivo maturation by performing gain- and loss-of-function studies in inducible Pax3 (iPax3) myogenic progenitors. Transplantation studies revealed that Notch1 signaling did not change the number of donor-derived fibers; however, the NOTCH1 overexpression cohorts showed enhanced satellite cell engraftment and more mature fibers, as indicated by fewer fibers expressing the embryonic myosin heavy-chain isoform and more type IIX fibers. While donor-derived Pax7+ cells were detected in all transplants, in the absence of Notch1, secondary grafts exhibited a high fraction of these cells in the interstitial space, indicating that NOTCH1 is required for proper satellite cell homing. Transcriptional profiling of NOTCH1-modified donor-derived satellite cells suggests that this may be due to changes in the extracellular matrix organization, cell cycle, and metabolism.

特别声明

1、本文转载旨在传播信息,不代表本网站观点,亦不对其内容的真实性承担责任。

2、其他媒体、网站或个人若从本网站转载使用,必须保留本网站注明的“来源”,并自行承担包括版权在内的相关法律责任。

3、如作者不希望本文被转载,或需洽谈转载稿费等事宜,请及时与本网站联系。

4、此外,如需投稿,也可通过邮箱info@biocloudy.com与我们取得联系。