The nitroreductase system of inducible targeted ablation facilitates cell-specific regenerative studies in zebrafish.
The nitroreductase system of inducible targeted ablation facilitates cell-specific regenerative studies in zebrafish.
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DOI：
10.1016/j.ymeth.2013.03.017
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发表时间：
2013-08-15
期刊：
影响因子：
4.8
通讯作者：
Mumm, Jeff S.
中科院分区：
文献类型：
--
作者：
White, David T.;Mumm, Jeff S.
在20世纪之交，经典的再生生物学--研究小龙虾、蜗牛和浮萍等动物的组织/组织/肢体再生--引起了人们的极大关注。然而，托马斯·亨特·摩根等科学界名人最终转向了其他领域，因为他们得出结论，研究再生机制在很大程度上是难以解决的，超出了观察的兴趣。在21世纪之交，再生领域的研究活动重新活跃起来，这在很大程度上是由于培养的干细胞在修复治疗方法方面的“希望”。此外，基于基因组学的方法允许在几乎任何物种中进行复杂的遗传/分子操作，使生物再生生物学远远超出了观察的极限。纵观其历史，复杂的范例，如肢体再生--涉及多种组织/细胞类型，因此可能涉及多种干细胞亚型--一直主导着再生生物学领域。相反，细胞再生--特定细胞类型的替换--只从几个角度进行了研究(主要是肌肉和机械感觉毛细胞)。然而，再生生物学希望解决的许多退行性疾病涉及单个细胞类型的丧失；因此，胚胎/诱导干细胞领域的一个主要重点是确定促进细胞特异性分化的培养条件。在这里，我们将讨论促进细胞特异性再生研究的最新方法。这样的范例可以揭示特定细胞类型的分化和离散干细胞利基的再生潜力是如何受到调控的。特别是，我们将重点介绍硝酸还原酶(NTR)系统如何促进可诱导的靶向细胞消融：1)大规模的遗传和化学筛选，以识别调节再生的因素；2)体内的时移成像实验，旨在更直接地研究再生过程。将强大的筛查和成像技术与靶向消融系统相结合，可以扩大我们对单个干细胞生态位如何受到调控的理解。前者促进了旨在增强人类再生潜力的治疗方法的发展，后者促进了对原本难以解决的现象的研究，例如细胞转分化或先天性免疫系统在再生范例中的作用。
At the turn of the 20th century, classical regenerative biology – the study of organismal/tissue/limb regeneration in animals such as crayfish, snails, and planaria – garnered much attention. However, scientific luminaries such as Thomas Hunt Morgan eventually turned to other fields after concluding that inquiries into regenerative mechanisms were largely intractable beyond observational intrigues. The field of regeneration has enjoyed a resurgence in research activity at the turn of the 21st century, in large part due to “the promise” of cultured stem cells regarding reparative therapeutic approaches. Additionally, genomics-based methods that allow sophisticated genetic/molecular manipulations to be carried out in nearly any species have extended organismal regenerative biology well beyond observational limits. Throughout its history, complex paradigms such as limb regeneration – involving multiple tissue/cell types, thus, potentially multiple stem cell subtypes – have predominated the regenerative biology field. Conversely, cellular regeneration – the replacement of specific cell types – has been studied from only a few perspectives (predominantly muscle and mechanosensory hair cells). Yet, many of the degenerative diseases that regenerative biology hopes to address involve the loss of individual cell types; thus, a primary emphasis of the embryonic/induced stem cell field is defining culture conditions which promote cell-specific differentiation. Here we will discuss recent methodological approaches that promote the study of cell-specific regeneration. Such paradigms can reveal how the differentiation of specific cell types and regenerative potential of discrete stem cell niches are regulated. In particular, we will focus on how the nitroreductase (NTR) system of inducible targeted cell ablation facilitates: 1) large-scale genetic and chemical screens for identifying factors that regulate regeneration and, 2) in vivo time-lapse imaging experiments aimed at investigating regenerative processes more directly. Combining powerful screening and imaging technologies with targeted ablation systems can expand our understanding of how individual stem cell niches are regulated. The former approach promotes the development of therapies aimed at enhancing regenerative potentials in humans, the latter facilitates investigation of phenomena that are otherwise difficult to resolve, such as the role of cellular transdifferentiation or the innate immune system in regenerative paradigms.
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DOI：
10.1007/s10162-002-3022-x
发表时间：
2003-06-01
影响因子：
2.4
作者：
Harris, JA;Cheng, AG;Rubel, EW
通讯作者：
Rubel, EW
影响因子：
4.5
作者：
Behra M;Bradsher J;Sougrat R;Gallardo V;Allende ML;Burgess SM
通讯作者：
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影响因子：
8.4
作者：
Bridgewater, JA;Springer, CJ;Collins, MK
通讯作者：
Collins, MK
影响因子：
2.7
作者：
Davison, Jon M.;Akitake, Courtney M.;Parsons, Michael J.
通讯作者：
Parsons, Michael J.
影响因子：
3
作者：
Hu, Shao-Yang;Lin, Pei-Yu;Wu, Jen-Leih
通讯作者：
Wu, Jen-Leih