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

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.Video abstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJlMzMxMTA3ZmQ5ODNiMzUyYWVkZjhjZjQ5MTQzNGEyMSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNzAyNzk4NjYxfQ.RxC6vnvo6G9CPgW1q6_VRqZH6ombzeG5hH-BwzrhQ34tKGGGCEsxxouQPwdDIvKcPBjdEKHBcb5Ndhi6cNT2xj6f2rAYJU3drVpRXq_fOhOWa1ZJKoG1hi0WrHXJAlFw7CjZyRjKfuniK9zrfqTloKFSho9aq3BhjuKe1_TIAKdhx_LtdUB4pSt_QpzifLIrEWZoLHxPmYi_R2Jw_vk96f0OTKaw8_hTZ0dfXj4SPG-G7fK4S0v6ynVXc8vy5UihHKDf4Nq9RfqGdAV3QZ2mk71Rz8dLE8Ju3cq3luH6ooT8FOBc6vF1N-vqt6_oU7fUBfPEubz6KeFoOHFtG2XYKA(mp4, (58.92 MB) Download video