Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment.

Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment.
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人类多能干细胞衍生的肌源祖细胞在植入后成熟为静止卫星细胞。

DOI:
10.1016/j.stem.2022.03.004
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发表时间:
2022-04-07
期刊:
影响因子:
23.9
通讯作者:
Kwon, Chulan
Kwon, Chulan
中科院分区:
医学1区
文献类型:
--
作者:
Sun, Congshan;Kannan, Suraj;Choi, In Young;Lim, HoTae;Zhang, Hao;Chen, Grace S.;Zhang, Nancy;Park, Seong-Hyun;Serra, Carlo;Iyer, Shama R.;Lloyd, Thomas E.;Lovering, Richard M.;Bin Lim, Su;Andersen, Peter;Wagner, Kathryn R.;Lee, Gabsang;Kwon, Chulan

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人多能干细胞(hPSC)衍生的肌源性祖细胞(MPC)移植是治疗多种退行性肌肉疾病的一种很有前途的方法。在这里,使用MPC特异性荧光报告系统(PAX7::GFP),我们证明了hpsc来源的MPC可以促进局部损伤小鼠和肌营养不良蛋白(mdx)缺乏小鼠的肌纤维再生。在mdx小鼠模型中,我们还证明了PAX7::GFP MPCs的一个子集在再生肌纤维的基底层植入,采用静止状态,并有助于再损伤时的再生。PAX7::GFP MPCs亚群经历成熟过程,并在体内植入后重塑其分子特征,类似于晚期胎儿MPCs/成人卫星细胞。这些体内成熟的PAX7::GFP MPCs保留了细胞自主再生的能力,并可以在次级受体小鼠的生态位中重新填充,为未来基于hpsc的肌肉疾病细胞治疗提供了原理证明。Sun等人发现来源于hPSCs的肌源性祖细胞在移植后可以在体内移植并成熟为局部卫星细胞。这些移植的MPCs不仅在肌肉再生中具有卫星细胞的功能,而且可以改善DMD小鼠模型的疾病表型。
Human pluripotent stem cell (hPSC) derived myogenic progenitor cell (MPC) transplantation is a promising therapeutic approach for a variety of degenerative muscle disorders. Here, using an MPC specific fluorescent reporter system (PAX7::GFP), we demonstrate that hPSC-derived MPCs can contribute to the regeneration of myofibers in mice following local injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal lamina of regenerated myofibers, adopt a quiescent state, and contribute to regeneration upon reinjury and in mdx mouse models. This subset of PAX7::GFP MPCs undergo a maturation process, and remodel their molecular characteristics to resemble late stage fetal MPCs/adult satellite cells following in vivo engraftment. These in vivo matured PAX7::GFP MPCs retain a cell autonomous ability to regenerate and can repopulate in niche of secondary recipient mice, providing a proof of principle for future hPSC-based cell therapy for muscle disorders. Sun et al., discover that myogenic progenitors derived from hPSCs could engraft and mature to become local satellite cells in vivo after transplantation. These engrafted MPCs not only function as satellite cells in muscle regeneration but also could ameliorate disease phenotype in DMD mouse model.
DOI: 10.1093/nar/gky1055
发表时间: 2019-01-08
影响因子: 14.9
作者:
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通讯作者: The Gene Ontology Consortium
DOI: 10.7554/elife.46981
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影响因子: 2.6
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期刊: STEM CELLS
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