A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion.
A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion.
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一个3D系统，用于建模人类胰腺发育及其参考单细胞转录组图集，并确定祖细胞扩展所需的信号通路。
DOI：
10.1038/s41467-021-23295-6
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发表时间：
2021-05-25
影响因子：
16.6
通讯作者：
Grapin-Botton A
中科院分区：
文献类型：
--
作者：
Gonçalves CA;Larsen M;Jung S;Stratmann J;Nakamura A;Leuschner M;Hersemann L;Keshara R;Perlman S;Lundvall L;Thuesen LL;Hare KJ;Amit I;Jørgensen A;Kim YH;Del Sol A;Grapin-Botton A
出于伦理和实践的原因，人类器官发生仍然相对未被探索。在这里，我们报告建立了一个单细胞转录组图谱的人胚胎胰腺在7到10周后发育。为了研究细胞间的相互作用，我们描述了Intercom，这是我们开发的用于识别受体-配体对及其下游效应的R-包。我们进一步报道了从胎儿组织或人类多能干细胞开始建立的人胰腺培养系统，使胰腺祖细胞能够在最小的、限定的三维介质中长期维持。对二维扩增的细胞和三维扩增到胎儿组织的细胞进行基准比较，发现三维扩增的祖细胞在转录上更接近胎儿胰腺。我们进一步证明了该系统作为筛查平台的潜力，并确定了EGF和成纤维细胞生长因子通路控制人类胰腺前体细胞扩增的重要性。从单细胞转录组分析到定义球体的培养液，作者提供了一份信息普查，以了解人类胰腺前体细胞的发育。这一方法确定了调控祖细胞增殖的信号通路(EGF和FGFs)。
Human organogenesis remains relatively unexplored for ethical and practical reasons. Here, we report the establishment of a single-cell transcriptome atlas of the human fetal pancreas between 7 and 10 post-conceptional weeks of development. To interrogate cell–cell interactions, we describe InterCom, an R-Package we developed for identifying receptor–ligand pairs and their downstream effects. We further report the establishment of a human pancreas culture system starting from fetal tissue or human pluripotent stem cells, enabling the long-term maintenance of pancreas progenitors in a minimal, defined medium in three-dimensions. Benchmarking the cells produced in 2-dimensions and those expanded in 3-dimensions to fetal tissue identifies that progenitors expanded in 3-dimensions are transcriptionally closer to the fetal pancreas. We further demonstrate the potential of this system as a screening platform and identify the importance of the EGF and FGF pathways controlling human pancreas progenitor expansion. From single-cell transcriptome analyses to defining culture media for spheroids, the authors provide a census of information to understand the development of human pancreatic progenitors. This approach identifies signalling pathways (EGF and FGF) regulating progenitor proliferation.
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影响因子：
2.5
作者：
Castaing, M;Duvillié, B;Scharfmann, R
通讯作者：
Scharfmann, R
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
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Yanai I
影响因子：
3.2
作者：
Hald, Jacob;Sprinkel, Anne Ejrnaes;Madsen, Ole D.
通讯作者：
Madsen, Ole D.
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
16.6
作者：
Byrnes LE;Wong DM;Subramaniam M;Meyer NP;Gilchrist CL;Knox SM;Tward AD;Ye CJ;Sneddon JB
通讯作者：
Sneddon JB