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Accession PRJCA004336
Title Sequential progenitor states mark the generation of pancreatic endocrine lineages in mice and humans
Relevance Medical
Data types Transcriptome or Gene expression
Organisms Homo sapiens
Description The pancreatic islet contains multiple hormone+ endocrine lineages (alpha, beta, delta, PP and epsilon cells), but the developmental processes that underlie endocrinogenesis are poorly understood. Here, we generated novel mouse lines and combined them with various genetic tools to enrich all types of hormone+ cells for well-based deep single-cell RNA sequencing (scRNA-seq), and gene coexpression networks were extracted from the generated data for the optimization of high-throughput droplet-based scRNA-seq analyses. These analyses defined an entire endocrinogenesis pathway in which different states of endocrine progenitor (EP) cells sequentially differentiate into specific endocrine lineages in mice. Subpopulations of the EP cells at the final stage (EP4early and EP4late) show different potentials for distinct endocrine lineages. epsilon cells and an intermediate cell population were identified as distinct progenitors that independently generate both alpha and PP cells. Single-cell analyses were also performed to delineate the human pancreatic endocrinogenesis process. Although the developmental trajectory of pancreatic lineages is generally conserved between humans and mice, clear interspecies differences, including differences in the proportions of cell types and the regulatory networks associated with the differentiation of specific lineages, have been detected. Our findings support a model in which sequential transient progenitor cell states determine the differentiation of multiple cell lineages and provide a blueprint for directing the generation of pancreatic islets in vitro.
Sample scope Single cell
Release date 2021-04-27
Publication
PubMed ID Article title Journal name DOI Year
33692492 Sequential progenitor states mark the generation of pancreatic endocrine lineages in mice and humans Cell Research 10.1038/s41422-021-00486-w 2021
37117185 USP7 controls NGN3 stability and pancreatic endocrine lineage development Nature Communications 10.1038/s41467-023-38146-9 2023
36113773 A transcriptional cross species map of pancreatic islet cells Molecular Metabolism 10.1016/j.molmet.2022.101595 2022
36513063 Single-cell transcriptomic and spatial landscapes of the developing human pancreas Cell Metabolism 10.1016/j.cmet.2022.11.009 2023
37660175 Deciphering early human pancreas development at the single-cell level Nature Communications 10.1038/s41467-023-40893-8 2023
37040771 Understanding cell fate acquisition in stem-cell-derived pancreatic islets using single-cell multiome-inferred regulomes Developmental Cell 10.1016/j.devcel.2023.03.011 2023
A multimodal cross-species comparison of pancreas development Research Square 10.21203/rs.3.rs-4151759/v1 2024
Grants
Agency program Grant ID Grant title
Ministry of Science and Technology of the People's Republic of China (MOST) National Key Research and Development Program of China 2019YFA0801500
Ministry of Science and Technology of the People's Republic of China (MOST) National Basic Research Program of China (973 Program) 2015CB942800
National Natural Science Foundation of China (NSFC) 31521004
National Natural Science Foundation of China (NSFC) 31471358
National Natural Science Foundation of China (NSFC) 31522036
National Natural Science Foundation of China (NSFC) 32030034
National Natural Science Foundation of China (NSFC) 32000566
China Postdoctoral Science Foundation BX20190009
China Postdoctoral Science Foundation 2020TQ0018
Submitter Cheng-Ran Xu (cxu@pku.edu.cn)
Organization Peking University
Submission date 2021-01-23

Project Data

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