| 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 |
|
| 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 |
