Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells.

IF 4.3 Q1 BIOCHEMICAL RESEARCH METHODS
Cell Reports Methods Pub Date : 2024-11-18 Epub Date: 2024-11-07 DOI:10.1016/j.crmeth.2024.100897
Pingxin Sun, Yuan Yuan, Zhuman Lv, Xinlu Yu, Haoxin Ma, Shulong Liang, Jiqianzhu Zhang, Jiangbo Zhu, Junyu Lu, Chunyan Wang, Le Huan, Caixia Jin, Chao Wang, Wenlin Li
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引用次数: 0

Abstract

Progress has been made in generating spinal cord and trunk derivatives from neuromesodermal progenitors (NMPs). However, maintaining the self-renewal of NMPs in vitro remains a challenge. In this study, we developed a cocktail of small molecules and growth factors that induces human embryonic stem cells to produce self-renewing NMPs (srNMPs) under chemically defined conditions. These srNMPs maintain the state of neuromesodermal progenitors in prolonged culture and have the potential to generate mesodermal cells and neurons, even at the single-cell level. Additionally, suspended srNMP aggregates can spontaneously differentiate into all tissue types of early embryonic trunks. Furthermore, transplanted srNMP-derived muscle satellite cells or progenitors of motor neurons were integrated into skeletal muscle or the spinal cord, respectively, and contributed to regeneration in mouse models. In summary, srNMPs hold great promise for applications in developmental biology and as renewable cell sources for cell therapy for trunk and spinal cord injuries.

从人类胚胎干细胞中产生具有神经元和骨骼肌双潜能的自我更新神经表皮祖细胞。
从神经表皮祖细胞(NMPs)生成脊髓和躯干衍生物的工作已取得进展。然而,维持 NMPs 在体外的自我更新仍是一项挑战。在这项研究中,我们开发了一种小分子和生长因子鸡尾酒,可诱导人类胚胎干细胞在化学定义的条件下产生自我更新的NMPs(srNMPs)。这些srNMPs在长期培养过程中能保持神经表皮祖细胞的状态,甚至在单细胞水平上也有生成中胚层细胞和神经元的潜力。此外,悬浮的 srNMP 聚集体可自发分化成早期胚胎干的所有组织类型。此外,移植的 srNMP 衍生肌肉卫星细胞或运动神经元祖细胞可分别整合到骨骼肌或脊髓中,并有助于小鼠模型的再生。总之,srNMPs 在发育生物学中的应用前景广阔,也是躯干和脊髓损伤细胞疗法的可再生细胞来源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Reports Methods
Cell Reports Methods Chemistry (General), Biochemistry, Genetics and Molecular Biology (General), Immunology and Microbiology (General)
CiteScore
3.80
自引率
0.00%
发文量
0
审稿时长
111 days
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