Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential.
Running the full human developmental clock in interspecies chimeras using alternative human stem cells with expanded embryonic potential.
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使用具有扩展的胚胎潜力的替代人类干细胞在种间嵌合体中运行人体发育时钟。
DOI：
10.1038/s41536-021-00135-1
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发表时间：
2021-05-17
影响因子：
7.2
通讯作者：
Zambidis ET
中科院分区：
文献类型：
--
作者：
Thomas J;Zimmerlin L;Huo JS;Considine M;Cope L;Zambidis ET
人类多能干细胞（hPSCs）可以产生特化的细胞系，在再生治疗和疾病建模方面具有巨大的潜力。然而，常规hPSC体外培养产生的谱系的发育阶段在表型上是胚胎阶段，可能不具备成年受体体内矫正再生功能所需的细胞成熟度。在这里，我们提出了成人组织如何产生人-动物种间嵌合体的科学证据来解决这个问题。首先，我们回顾了体外和通过类器官技术从常规hPSC分化出的胚胎谱系的表型，并比较了它们与正常人类子宫、胎儿和成人发育过程中产生的组织的功能相关性。我们假设胚胎期hpsc分化细胞移植到受体成人宿主生态位的发育不一致是最终限制其在细胞治疗和成人疾病建模中的应用的重要机制。我们提出，这种发育障碍可以通过优化的种间嵌合体来克服，这种嵌合体允许在与人类相容的妊娠时间框架内，在动物宿主体内产生成人阶段、患者特异性的完整器官。我们认为，要实现这一目标，最终可能需要等待衍生出具有改进的胚胎嵌合体能力的替代的、原始的全能样干细胞。我们回顾了衍生具有扩展胚胎潜力的替代人类干细胞状态的科学挑战，概述了在适当的伦理和监管监督下进行这一新兴研究的前进道路，并为为什么当前联邦政府对这一重要生物医学研究类别的资助限制应该放开进行辩护。
Human pluripotent stem cells (hPSCs) can generate specialized cell lineages that have great potential for regenerative therapies and disease modeling. However, the developmental stage of the lineages generated from conventional hPSC cultures in vitro are embryonic in phenotype, and may not possess the cellular maturity necessary for corrective regenerative function in vivo in adult recipients. Here, we present the scientific evidence for how adult human tissues could generate human–animal interspecific chimeras to solve this problem. First, we review the phenotypes of the embryonic lineages differentiated from conventional hPSC in vitro and through organoid technologies and compare their functional relevance to the tissues generated during normal human in utero fetal and adult development. We hypothesize that the developmental incongruence of embryo-stage hPSC-differentiated cells transplanted into a recipient adult host niche is an important mechanism ultimately limiting their utility in cell therapies and adult disease modeling. We propose that this developmental obstacle can be overcome with optimized interspecies chimeras that permit the generation of adult-staged, patient-specific whole organs within animal hosts with human-compatible gestational time-frames. We suggest that achieving this goal may ultimately have to await the derivation of alternative, primitive totipotent-like stem cells with improved embryonic chimera capacities. We review the scientific challenges of deriving alternative human stem cell states with expanded embryonic potential, outline a path forward for conducting this emerging research with appropriate ethical and regulatory oversight, and defend the case of why current federal funding restrictions on this important category of biomedical research should be liberalized.
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驯化食蟹猴胚胎干细胞可产生新生种间嵌合猪
影响因子：
21.1
作者：
Fu, Rui;Yu, Dawei;Zhou, Qi
通讯作者：
Zhou, Qi
影响因子：
4.6
作者：
Franziska Fuhrmann, Jana;Buono, Lorena;Centanin, Lazaro
通讯作者：
Centanin, Lazaro
DOI：
10.1242/dev.164368
发表时间：
2018-06-26
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Ebisuya M;Briscoe J
通讯作者：
Briscoe J
影响因子：
5.9
作者：
Brooks, Matthew J.;Chen, Holly Y.;Swaroop, Anand
通讯作者：
Swaroop, Anand
影响因子：
7.7
作者：
Dye BR;Hill DR;Ferguson MA;Tsai YH;Nagy MS;Dyal R;Wells JM;Mayhew CN;Nattiv R;Klein OD;White ES;Deutsch GH;Spence JR
通讯作者：
Spence JR