Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Cell Metab. 2023 Nov 7;35(11):1944-1960.e7. doi: 10.1016/j.cmet.2023.10.001. Epub 2023 Oct 27.
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.
人类胰腺的可塑性从多个单细胞 RNA 测序 (scRNA-seq) 研究中得到暗示。然而，这些研究无一例外地基于静态数据集，只能通过拟时估计来推断命运轨迹。此外，对分离胰岛的分析导致其他细胞类型严重代表性不足，阻碍了我们探究外分泌-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一个机会，可以在单细胞水平上动态跟踪组织的可塑性。将来自具有或不具有已知再生刺激 (BMP 信号) 的同一供体 HPS 在不同时间点的数据集进行组合，生成了存储真实时间或治疗依赖性信息的整合单细胞数据集。这种整合揭示了与导管祖细胞激活一致的群体转移、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产生细胞的检测。这项研究提供了对整个人类胰腺组织的首次纵向 scRNA-seq 分析，以动态方式证实了其可塑性。
