小柯机器人

美国迈阿密大学Juan Domínguez-Bendala等研究人员合作发现，活体胰腺切片的动态scRNA序列分析揭示了功能性内分泌细胞在导管-腺泡中间阶段的新生过程。2023年10月27日，《细胞—代谢》杂志在线发表了这项成果。

研究人员表示，多项单细胞RNA测序（scRNA-seq）研究暗示了人类胰腺的可塑性。然而，这些研究无一例外都是基于静态数据集，而命运轨迹只能通过伪时间估计来推断。此外，对离体胰岛的分析导致其他细胞类型的代表性严重不足，阻碍了人们研究外分泌-内分泌相互作用的能力。

人类胰腺切片（HPS）的长期培养为该领域提供了在单细胞水平动态跟踪组织可塑性的机会。将不同时间点的相同供体胰腺切片数据集与已知的再生刺激（BMP信号）或不刺激的数据集结合起来，就能获得整合的单细胞数据集，从而存储真正的时间或治疗依赖性信息。这种整合揭示了与导管祖细胞活化、导管/腺泡边界模糊、导管-腺泡-内分泌分化轴的形成以及过渡性胰岛素分泌细胞的检测相一致的群体变化。这项研究首次对整个人类胰腺组织进行了纵向scRNA-seq分析，证实了胰腺组织的动态可塑性。

附：英文原文

Title: Dynamic scRNA-seq of live human pancreatic slices reveals functional endocrine cell neogenesis through an intermediate ducto-acinar stage

Author: Mayur Doke, Silvia álvarez-Cubela, Dagmar Klein, Isabella Altilio, Joseph Schulz, Luciana Mateus Gonalves, Joana Almaa, Christopher A. Fraker, Alberto Pugliese, Camillo Ricordi, Mirza M.F. Qadir, Ricardo L. Pastori, Juan Domínguez-Bendala

Issue&Volume: 2023-10-27

Abstract: Human pancreatic plasticity is implied from multiple single-cell RNA sequencing (scRNA-seq) studies. However, these have been invariably based on static datasets from which fate trajectories can only be inferred using pseudotemporal estimations. Furthermore, the analysis of isolated islets has resulted in a drastic underrepresentation of other cell types, hindering our ability to interrogate exocrine-endocrine interactions. The long-term culture of human pancreatic slices (HPSs) has presented the field with an opportunity to dynamically track tissue plasticity at the single-cell level. Combining datasets from same-donor HPSs at different time points, with or without a known regenerative stimulus (BMP signaling), led to integrated single-cell datasets storing true temporal or treatment-dependent information. This integration revealed population shifts consistent with ductal progenitor activation, blurring of ductal/acinar boundaries, formation of ducto-acinar-endocrine differentiation axes, and detection of transitional insulin-producing cells. This study provides the first longitudinal scRNA-seq analysis of whole human pancreatic tissue, confirming its plasticity in a dynamic fashion.

DOI: 10.1016/j.cmet.2023.10.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00370-4

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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