Embryonic origin of adult stem cells required for tissue homeostasis and regeneration.
Embryonic origin of adult stem cells required for tissue homeostasis and regeneration.
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DOI：
10.7554/elife.21052
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发表时间：
2017-01-10
期刊：
影响因子：
7.7
通讯作者：
Alvarado AS
中科院分区：
文献类型：
--
作者：
Davies EL;Lei K;Seidel CW;Kroesen AE;McKinney SA;Guo L;Robb SM;Ross EJ;Gotting K;Alvarado AS
Planarian neoblast是多能性成体干细胞和谱系引发的祖细胞，其是产生和维持所有分化的细胞类型（包括种系）所需的。新生细胞最初被定义为存在于成体实质中的未分化细胞，经常被比作胚胎干细胞，但其发育起源仍然不清楚。我们调查了Schmidtea mediterranea胚胎发生过程中neoblasts的来源，并报告说，neoblasts来自一个无政府状态，循环piwi-1+人口完全负责生产的所有临时和永久性器官在胚胎发生过程中。早期胚胎piwi-1+细胞在分子和功能上与新成细胞不同：它们表达独特的早期胚胎富集转录物群，并且在细胞移植试验中表现出与新成细胞不同的行为。新生细胞谱系随着器官发生开始而出现，并且是胚胎发生期间所有主要器官系统的构建所必需的。这些亚群在成年期不断产生，在那里它们充当组织稳态和再生的代理人。http://dx.doi.org/10.7554/eLife.21052.001扁平虫是再生的大师。只要切下扁形虫的任何一部分，两周内就会长出一个功能齐全的新个体。这不是一项简单的任务，因为扁形虫含有各种各样的器官系统，包括大脑，神经系统，眼睛，肾脏，肠道，肌肉和皮肤。扁形虫的再生能力归功于称为新胚细胞的成体干细胞。像胚胎干细胞一样，新母细胞可以自我复制，它们可以发育成成虫中发现的任何类型的细胞。相比之下，果蝇、斑马鱼、小鼠和人类的成体干细胞只能产生它们所生活的器官或组织中的细胞类型。现在，Davies等人通过记录扁虫胚胎在不同发育阶段的不同基因表达特征，追踪了扁虫物种Schmidtea mediathea胚胎中新母细胞的发育方式和时间。同时还绘制了一个基因图谱，这些基因在胚胎组织和开始发育的主要器官中表达。这些工具和细胞移植实验的结果表明，当主要器官开始形成时，新母细胞从胚胎干细胞中出现。当新生的新母细胞开始表达与成年新母细胞相同的基因组合时，它们也开始表现得像这些细胞一样。在扁虫的整个生命过程中，新成细胞的群体仍然存在，帮助维持，修复和再生组织。在未来，建立在Davies等人的研究结果基础上的工作将有助于研究人员更多地了解干细胞是如何维持和调节的。通过更多地了解新母细胞和人类成体干细胞之间的遗传差异，科学家们可能能够解释为什么人类和其他哺乳动物的再生能力有限。这些信息可能有助于开发刺激退行性疾病或创伤性损伤患者再生的治疗方法。DOI：http://dx.doi.org/10.7554/eLife.21052.002网站
Planarian neoblasts are pluripotent, adult somatic stem cells and lineage-primed progenitors that are required for the production and maintenance of all differentiated cell types, including the germline. Neoblasts, originally defined as undifferentiated cells residing in the adult parenchyma, are frequently compared to embryonic stem cells yet their developmental origin remains obscure. We investigated the provenance of neoblasts during Schmidtea mediterranea embryogenesis, and report that neoblasts arise from an anarchic, cycling piwi-1+ population wholly responsible for production of all temporary and definitive organs during embryogenesis. Early embryonic piwi-1+ cells are molecularly and functionally distinct from neoblasts: they express unique cohorts of early embryo enriched transcripts and behave differently than neoblasts in cell transplantation assays. Neoblast lineages arise as organogenesis begins and are required for construction of all major organ systems during embryogenesis. These subpopulations are continuously generated during adulthood, where they act as agents of tissue homeostasis and regeneration. DOI: http://dx.doi.org/10.7554/eLife.21052.001 Flatworms are masters of regeneration. If virtually any piece of a flatworm is cut off, a new fully functional individual will grow from it within two weeks. This is no simple task since flatworms contain a wide variety of organ systems, including a brain, nervous system, eyes, kidneys, gut, muscle and skin. Flatworms owe their regenerative abilities to adult stem cells called neoblasts. Like embryonic stem cells, neoblasts can replicate themselves and they can develop into any type of cell found in an adult worm. In contrast, adult stem cells in fruit flies, zebrafish, mice and humans can only produce the type of cells found in the organ or tissue they live in. Now, Davies et al. have tracked how and when neoblasts develop in embryos of the flatworm species Schmidtea mediterranea by documenting the distinct gene expression signatures in flatworm embryos at various stages of development. An atlas of the genes that are expressed in various embryonic tissues and in major organs as they begin to develop was also created. These tools, and the results of cell transplantation experiments, revealed that neoblasts emerge from embryonic stem cells as the major organs start to form. As the emerging neoblasts start to express the same combination of genes as adult neoblasts, they also begin to behave just like these cells. The populations of neoblasts remain present throughout the life of the flatworm, helping to maintain, repair and regenerate tissues. In the future, work that builds on the results presented here by Davies et al. will help researchers to understand more about how stem cells are maintained and regulated. By learning more about the genetic differences between neoblasts and human adult stem cells scientists may be able to explain why humans and other mammals have a limited ability to regenerate. This information could potentially help to develop treatments that stimulate regeneration in patients with degenerative diseases or traumatic injuries. DOI: http://dx.doi.org/10.7554/eLife.21052.002