Position-dependent plasticity of distinct progenitor types in the primitive streak.
Position-dependent plasticity of distinct progenitor types in the primitive streak.
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DOI：
10.7554/elife.10042
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发表时间：
2016-01-18
期刊：
影响因子：
7.7
通讯作者：
Wilson V
中科院分区：
文献类型：
--
作者：
Wymeersch FJ;Huang Y;Blin G;Cambray N;Wilkie R;Wong FC;Wilson V
喙尾（头到尾）轴由胚胎尾端的祖细胞群体提供。尽管最近的进展，这些人群之一，神经中胚层祖细胞，他们的性质和其他人群的关系仍然不清楚。在这里，我们表明，neuromesodermal祖细胞是一个单一的Sox2lowTlow实体，其选择的神经或中胚层的命运是由他们在祖细胞区域的位置。中胚层命运的选择是Wnt/β-连环蛋白依赖性的。Wnt/β-catenin信号传导也是在中干形成期间祖细胞扩增的先前未识别的阶段所需的。侧/腹侧中胚层祖细胞代表了一种独特的定向状态，即使在神经转录因子Sox 2过表达时也不能分化为神经命运。它们不需要Wnt/β-连环蛋白信号传导用于中胚层分化。该信息有助于正确解释体内遗传研究和开发用于产生临床感兴趣的生理学相关细胞群的体外方案。DOI：www.example.com我们的身体，就像所有有脊椎的动物一样，在胚胎发育过程中以头到尾的顺序形成。这一过程是由称为祖细胞的增殖细胞群推动的，祖细胞存在于称为原始条纹的早期胚胎结构中，后来在胚胎的尾端发现。其中一个群体-被称为神经中胚层祖细胞（或NMP）-产生动物的脊髓，肌肉和骨组织。然而，目前尚不清楚这些细胞群是如何维持的，或者是什么触发了这些细胞专门化为正确的细胞类型。甚至还不清楚NMPs是一种单细胞类型还是几种类型的祖细胞的集合，每种祖细胞在制造脊髓或肌肉和骨骼方面的倾向略有不同。解决这些问题可以为脊髓损伤等疾病的细胞替代疗法的未来发展提供信息。Wymeersch等人使用了一系列技术来鉴定、绘制命运图并评估原始条纹中祖细胞的发育潜力。这揭示了祖细胞区域中细胞所采用的命运的细微差异。然而，这些区域差异被发现是由于祖细胞对它们从环境中接收的信号做出反应的广泛能力，而不是被硬连接到祖细胞中。事实上，Wymeersch等人只检测到两种不同的细胞类型：NMPs和一种称为侧/近轴中胚层祖细胞（或LPMPs）的新细胞群，与NMPs不同，LPMPs不形成神经细胞。进一步的实验研究了这些祖细胞环境中存在的分子信号，这些信号有助于决定它们的命运。NMPs通过采取所谓的中胚层命运来响应称为Wnt的重要发育信号。该信号还诱导NMPs在动物身体形成期间经历先前未知的增殖阶段。另一方面，LPMP不需要Wnt来形成中胚层。这些发现表明，对胚胎的研究可以识别可能与临床相关的新的祖细胞群体，并揭示胚胎内细胞环境决定其命运的新方法。DOI：www.example.com网站
The rostrocaudal (head-to-tail) axis is supplied by populations of progenitors at the caudal end of the embryo. Despite recent advances characterising one of these populations, the neuromesodermal progenitors, their nature and relationship to other populations remains unclear. Here we show that neuromesodermal progenitors are a single Sox2lowTlow entity whose choice of neural or mesodermal fate is dictated by their position in the progenitor region. The choice of mesoderm fate is Wnt/β-catenin dependent. Wnt/β-catenin signalling is also required for a previously unrecognised phase of progenitor expansion during mid-trunk formation. Lateral/ventral mesoderm progenitors represent a distinct committed state that is unable to differentiate to neural fates, even upon overexpression of the neural transcription factor Sox2. They do not require Wnt/β-catenin signalling for mesoderm differentiation. This information aids the correct interpretation of in vivo genetic studies and the development of in vitro protocols for generating physiologically-relevant cell populations of clinical interest. DOI: http://dx.doi.org/10.7554/eLife.10042.001 Our bodies, like those of all animals with a backbone, form during embryo development in a head-to-tail sequence. This process is fuelled by populations of proliferating cells called progenitor cells, which are found in an early embryonic structure called the primitive streak, and later at the tail-end of the embryo. One of these populations – known as the neuromesodermal progenitors (or NMPs) – produces the animal’s spinal cord, muscle and bone tissue. However, it is not clear how this cell population is maintained or what triggers these cells to specialise into the correct cell type. It is even unclear whether NMPs are a single cell type or a collection of several types of progenitor, each with a slightly different propensity to make spinal cord or muscle and bone. Answering these questions could inform the future development of cell-replacement therapies for conditions such as spinal injuries. Wymeersch et al. used a range of techniques to identify, map the fate, and assess the developmental potential of progenitors in the primitive streak. This revealed fine-grained differences in the fates adopted by cells in the progenitor region. However, these regional differences were found to result from the progenitor cells’ extensive ability to respond to signals they receive from their environment, rather than being hard-wired into the progenitor cells. In fact, Wymeersch et al. detected only two distinct cell types: the NMPs and a new cell population termed lateral/paraxial mesoderm progenitors (or LPMPs), which, unlike NMPs, do not form nerve cells. Further experiments investigated the molecular signals present in the environment of these progenitors that help to decide their fate. NMPs respond to an important developmental signal, called Wnt, by adopting a so-called mesoderm fate. This signal also induces NMPs to undergo a previously unknown phase of proliferation during the formation of the animal’s body. LPMPs, on the other hand, do not require Wnt to form mesoderm. These findings show that studies with embryos can identify new progenitor populations that might be clinically relevant, and reveal new ways in which a cell’s environment inside an embryo can determine its fate. DOI: http://dx.doi.org/10.7554/eLife.10042.002