Characterization of hiPSC-Derived Muscle Progenitors Reveals Distinctive Markers for Myogenic Cell Purification Toward Cell Therapy.
Characterization of hiPSC-Derived Muscle Progenitors Reveals Distinctive Markers for Myogenic Cell Purification Toward Cell Therapy.
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DOI：
10.1016/j.stemcr.2021.03.004
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发表时间：
2021-04-13
影响因子：
5.9
通讯作者：
Sakurai H
中科院分区：
文献类型：
--
作者：
Nalbandian M;Zhao M;Sasaki-Honda M;Jonouchi T;Lucena-Cacace A;Mizusawa T;Yasuda M;Yoshida Y;Hotta A;Sakurai H
从人诱导多能干细胞（hiPSC）分化的肌肉祖细胞（MuPC）的移植是用于治疗骨骼肌疾病如杜氏肌营养不良症（DMD）的有前景的方法。然而，在移植前适当纯化MuPCs对于临床应用是必不可少的。在这里，通过使用MYF 5 hiPSC报告细胞系，我们鉴定了两种用于肌原性细胞纯化的标志物：CDH 13，其纯化了大部分肌原性细胞，和FGFR 4，其纯化了MuPC的子集。用每种标记物纯化的细胞在移植后显示出高的再生效率，并有助于DMD免疫缺陷模型小鼠中肌养蛋白表达的恢复。此外，我们发现MYF 5通过与启动子区域结合来调节CDH 13的表达。这些发现表明，FGFR 4和⑶ H 13是用于纯化hiPSC衍生的MuPC以用于治疗应用的强候选物。MYF 5和PAX 7标记不同的hiPSC-MuPC群体MYF 5+细胞的RNA测序揭示了CDH 13和FGFR 4作为hiPSC-MuPC标记物CDH 13+和FGFR 4 + hiPSC-MuPC有助于mdx小鼠中的再生MYF 5通过与其启动子区结合来调节CDH 13表达肌肉祖细胞（MuPC）的适当纯化是成功进行杜氏肌营养不良症细胞疗法的必要步骤。在这篇论文中，Nalbandian及其同事鉴定了两种表面标记物（FGFR 4和CDH 13），它们允许在hiPSC-肌肉祖细胞培养物中有效分离MuPC与非肌源性细胞。用这些标记物纯化的细胞显示出改善的生肌和再生能力。
The transplantation of muscle progenitor cells (MuPCs) differentiated from human induced pluripotent stem cells (hiPSCs) is a promising approach for treating skeletal muscle diseases such as Duchenne muscular dystrophy (DMD). However, proper purification of the MuPCs before transplantation is essential for clinical application. Here, by using MYF5 hiPSC reporter lines, we identified two markers for myogenic cell purification: CDH13, which purified most of the myogenic cells, and FGFR4, which purified a subset of MuPCs. Cells purified with each of the markers showed high efficiency for regeneration after transplantation and contributed to the restoration of dystrophin expression in DMD-immunodeficient model mice. Moreover, we found that MYF5 regulates CDH13 expression by binding to the promoter regions. These findings suggest that FGFR4 and CDH13 are strong candidates for the purification of hiPSC-derived MuPCs for therapeutical application. MYF5 and PAX7 mark different populations of hiPSC-MuPCs RNA-seq of MYF5+ cells reveals CDH13 and FGFR4 as hiPSC-MuPC markers CDH13+ and FGFR4+ hiPSC-MuPCs contribute to regeneration in mdx mice MYF5 regulates CDH13 expression by binding to its promoter region Proper purification of muscle progenitor cells (MuPCs) is a necessary step to succeed in cell therapy for Duchenne muscular dystrophy. In this paper, Nalbandian and colleagues identify two surface markers (FGFR4 and CDH13) that allow for the efficient separation of MuPCs from non-myogenic cells in hiPSC-muscle progenitor culture. Cells purified with these markers showed improved myogenic and regeneration capacity.
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影响因子：
2.7
作者：
Biressi, Stefano;Bjornson, Christopher R. R.;Carlig, Poppy M. M.;Nishijo, Koichi;Keller, Charles;Rando, Thomas A.
通讯作者：
Rando, Thomas A.
影响因子：
8.8
作者：
Magli A;Incitti T;Kiley J;Swanson SA;Darabi R;Rinaldi F;Selvaraj S;Yamamoto A;Tolar J;Yuan C;Stewart R;Thomson JA;Perlingeiro RCR
通讯作者：
Perlingeiro RCR
DOI：
10.1073/pnas.1808303116
发表时间：
2019-03-05
影响因子：
11.1
作者：
Incitti, Tania;Magli, Alessandro;Perlingeiro, Rita C. R.
通讯作者：
Perlingeiro, Rita C. R.
影响因子：
12.4
作者：
Negroni, Elisa;Riederer, Ingo;Mouly, Vincent
通讯作者：
Mouly, Vincent
影响因子：
5.9
作者：
Kim HS;Lee J;Lee DY;Kim YD;Kim JY;Lim HJ;Lim S;Cho YS
通讯作者：
Cho YS