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Single-cell analyses identify distinct and intermediate states of zebrafish pancreatic islet development.


ABSTRACT: Pancreatic endocrine islets are vital for glucose homeostasis. However, the islet developmental trajectory and its regulatory network are not well understood. To define the features of these specification and differentiation processes, we isolated individual islet cells from TgBAC(neurod1:EGFP) transgenic zebrafish and analyzed islet developmental dynamics across four different embryonic stages using a single-cell RNA-seq strategy. We identified proliferative endocrine progenitors, which could be further categorized by different cell cycle phases with the G1/S subpopulation displaying a distinct differentiation potential. We identified endocrine precursors, a heterogeneous intermediate-state population consisting of lineage-primed alpha, beta and delta cells that were characterized by the expression of lineage-specific transcription factors and relatively low expression of terminally differentiation markers. The terminally differentiated alpha, beta, and delta cells displayed stage-dependent differentiation states, which were related to their functional maturation. Our data unveiled distinct states, events and molecular features during the islet developmental transition, and provided resources to comprehensively understand the lineage hierarchy of islet development at the single-cell level.

SUBMITTER: Lu CJ 

PROVIDER: S-EPMC6604604 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Single-cell analyses identify distinct and intermediate states of zebrafish pancreatic islet development.

Lu Chong-Jian CJ   Fan Xiao-Ying XY   Guo Yue-Feng YF   Cheng Zhen-Chao ZC   Dong Ji J   Chen Jin-Zi JZ   Li Lian-Yan LY   Wang Mei-Wen MW   Wu Ze-Kai ZK   Wang Fei F   Tong Xiang-Jun XJ   Luo Ling-Fei LF   Tang Fu-Chou FC   Zhu Zuo-Yan ZY   Zhang Bo B  

Journal of molecular cell biology 20190601 6


Pancreatic endocrine islets are vital for glucose homeostasis. However, the islet developmental trajectory and its regulatory network are not well understood. To define the features of these specification and differentiation processes, we isolated individual islet cells from TgBAC(neurod1:EGFP) transgenic zebrafish and analyzed islet developmental dynamics across four different embryonic stages using a single-cell RNA-seq strategy. We identified proliferative endocrine progenitors, which could b  ...[more]

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