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发育中的人类胰腺的单细胞转录组和空间格局
2022-12-13 15:15

英国伦敦国王学院Shanta J. Persaud研究组揭示了发育中的人类胰腺的单细胞转录组和空间格局。相关论文于2022年12月12日发表于国际顶尖学术期刊《细胞—代谢》杂志。

他们进行了发育中的人类胰腺的各种细胞类型的详细转录组分析,包括它们的空间基因模式。他们将多个发育时间点的单细胞RNA测序与空间转录组学相结合,揭示了不同的时空基因级联。细胞轨迹推断确定了内分泌祖细胞群和分支特异性基因,因为祖细胞分化为α或β细胞。空间分化轨迹显示Schwann细胞与内分泌祖细胞在空间上共定位,细胞-细胞连通性分析预测它们可能通过L1CAM-EPHB2信号相互作用。

他们的综合方法使人们能够识别间质内的异质性和多谱系动态,表明它有助于外分泌腺泡细胞状态。最后,他们为研究界生成了一个研究人类胰腺发育的交互式网络资源。

据了解,目前的分化方案还没有成功地在体外复制生成功能齐全的人类β细胞,部分原因是对人类胰腺发育的不完全了解。

附:英文原文

Title: Single-cell transcriptomic and spatial landscapes of the developing human pancreas

Author: Oladapo Edward Olaniru, Ulrich Kadolsky, Shichina Kannambath, Heli Vaikkinen, Kathy Fung, Pawan Dhami, Shanta J. Persaud

Issue&Volume: 2022-12-12

Abstract: Current differentiation protocols have not been successful in reproducibly generating fully functional human beta cells in vitro, partly due to incomplete understanding of human pancreas development. Here, we present detailed transcriptomic analysis of the various cell types of the developing human pancreas, including their spatial gene patterns. We integrated single-cell RNA sequencing with spatial transcriptomics at multiple developmental time points and revealed distinct temporal-spatial gene cascades. Cell trajectory inference identified endocrine progenitor populations and branch-specific genes as the progenitors differentiate toward alpha or beta cells. Spatial differentiation trajectories indicated that Schwann cells are spatially co-located with endocrine progenitors, and cell-cell connectivity analysis predicted that they may interact via L1CAM-EPHB2 signaling. Our integrated approach enabled us to identify heterogeneity and multiple lineage dynamics within the mesenchyme, showing that it contributed to the exocrine acinar cell state. Finally, we have generated an interactive web resource for investigating human pancreas development for the research community.

DOI: 10.1016/j.cmet.2022.11.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00500-9

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:31.373
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Online/在线发表

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