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Updated: Jun 22, 2026
Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
Published on: September 30, 2018
DTA-mediated targeted ablation revealed differential interdependence of endocrine cell lineages in early development
Zhen Li1, Vladimir Korzh, Zhiyuan Gong
1Department of Biological Sciences, National University of Singapore, 119260 Singapore, Singapore.
Abstract:
Cell lineage analysis is critical in understanding the relationship between progenitors and differentiated cells as well as the mechanism underlying the process of differentiation. In order to study the zebrafish endocrine pancreas cell lineage, transgenic expression of diphtheria toxin gene A chain (DTA) under two cell type-specific promoters derived from the insulin (ins) and somatostatin2 (sst2) genes was used to ablate the two types of endocrine cells: insulin-producing beta-cells and somatostatin-producing delta-cells, respectively. We found that ablation of beta-cells resulted in a reduction of not only beta-cells but also glucagon-producing alpha-cells; in contrast, delta-cells were largely unaffected. Ablation of delta-cells led to reduction of all three types of endocrine cells: alpha-, beta-, and delta. Interestingly, alpha-cells were more profoundly affected in both beta- and delta-cell ablations and were frequently reduced together with beta- and delta-cells. By taking advantage of Tg(ins:gfp) and Tg(sst2:gfp) lines, we also monitored the changes of different types of endocrine cells in vivo after ablation and found that both beta- and delta-cell populations significantly recovered by 3dpf after their ablation and it seemed that delta-cells had a better capability of recovery than beta-cells. Thus, our current observations indicated differential interdependence of these three cell lineages. The development of zebrafish alpha-cells, but not delta-cells, is dependent on beta-cells, while the development of both alpha- and beta-cells is dependent on delta-cells. In contrast, the development of delta-cells was independent of beta-cells.
Insights
Zebrafish endocrine pancreas cell development reveals distinct lineage dependencies. Alpha-cell development relies on beta-cells, while both alpha- and beta-cells depend on delta-cells for their growth.
Area of Science:
- Developmental Biology
- Endocrinology
- Zebrafish Models
Background:
- Understanding cell lineage relationships is crucial for deciphering differentiation mechanisms.
- The zebrafish endocrine pancreas, comprising alpha, beta, and delta cells, serves as a model for studying cell interactions.
- Previous studies have not fully elucidated the interdependence of these endocrine cell lineages.
Purpose of the Study:
- To investigate the interdependence of zebrafish alpha, beta, and delta cell lineages.
- To determine the role of specific cell types in the development and maintenance of other endocrine cell populations.
- To analyze the recovery capacity of different endocrine cell types following targeted ablation.
Main Methods:
- Utilized transgenic zebrafish expressing diphtheria toxin A chain (DTA) under cell-specific promoters (insulin and somatostatin2) for targeted cell ablation.
- Monitored changes in alpha, beta, and delta cell populations in vivo using Tg(ins:gfp) and Tg(sst2:gfp) reporter lines.
- Assessed cell population dynamics and recovery post-ablation at 3 days post-fertilization (dpf).
Main Results:
- Ablation of beta-cells reduced both beta- and alpha-cells, with minimal impact on delta-cells.
- Ablation of delta-cells led to the reduction of alpha-, beta-, and delta-cells, with alpha-cells being most profoundly affected.
- Both beta- and delta-cell populations showed significant recovery by 3 dpf, with delta-cells exhibiting a greater recovery capacity.
Conclusions:
- Zebrafish alpha-cell development is dependent on beta-cells, while delta-cells are essential for the development of both alpha- and beta-cells.
- Delta-cell development is independent of beta-cells.
- These findings highlight differential interdependence and distinct recovery capabilities among zebrafish endocrine pancreas cell lineages.
