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Spatial and transcriptional heterogeneity of pancreatic beta cell neogenesis revealed by a time-resolved reporter system – published online 03/03/2022

Sasaki graphical abstract

Shugo Sasaki, Michelle Y. Y. Lee, Yuka Wakabayashi, Luka Suzuki, Helena Winata, Miwa Himuro, Taka-aki Matsuoka, Iichiro Shimomura, Hirotaka Watada, Francis C. Lynn, Takeshi Miyatsuka

Although endocrine pancreas development has been investigated by many researchers, the beta cell developmental niche, or precisely where and when beta cells arise in vivo, remains less well described. Part of the reason for this is that there have been no methods to readily detect newly generated beta cells in situ. In this issue, Sasaki et al ( describe a novel time-resolved mouse model, which was developed to distinguish newborn beta cells from more differentiated beta cells. The authors report that this model provides the first in vivo evidence that beta cells arise from two distinct regions: ductal or blood vessel niches. Using this model, the authors also show that single-cell transcriptional heterogeneity during beta cell genesis correlates with the spatial heterogeneity. Furthermore, single-cell mRNA profiles of human embryonic stem cell-derived beta-like cells demonstrated a transcriptional similarity with the data from newborn beta cells in mice. The authors conclude that this work provides insight for the future development of regenerative therapies for diabetes.

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