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| Status |
Public on Jun 18, 2024 |
| Title |
Directed differentiation of pancreatic δ cells from human pluripotent stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Human pancreatic δ cells maintain the balance of pancreatic hormones and loss of δ cells or disruption of somatostatin release is associated with diabetes. Despite their important role, human δ cells are scarce (~5% within the islets), limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. In this study, we established a link between fibroblast growth factor (FGF) signaling pathways and pancreatic δ-cell lineage specification. FGF7 helped maintain a pancreatic endoderm/progenitor state with higher expression levels of PDX1 and CHGA, whereas FGF2 biased cells towards the pancreatic δ-cell lineage by inducing the expression of SST and the δ-cell specific transcription factor HHEX, via FGF receptor 1(FGFR1). We developed a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured b cells and mouse b cells upon transplantation. The generation of somatostatin-secreting pancreatic δ cells from human stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.
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| Overall design |
H1 ES cells were differentiated into delta cell-containing islet organoids. The Islet organoids were collected at S7D14 and analysed by scRNA-seq.
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| Web link |
http://DOI: 10.1038/s41467-024-50611-7
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| Contributor(s) |
Liu H, Chen L, Zhang T, Wang N |
| Citation(s) |
39068220 |
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| Submission date |
Jun 13, 2024 |
| Last update date |
Sep 19, 2024 |
| Contact name |
LIHUA CHEN |
| E-mail(s) |
chen_lihua@gzlab.ac.cn
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| Phone |
086-13724864235
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| Organization name |
Guangzhou Laboratory
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| Street address |
Guangzhou International Bioland
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510000 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1123647 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE269764_RAW.tar |
346.4 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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