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| Status |
Public on May 13, 2024 |
| Title |
Trefoil factor 2 expressed by the murine pancreatic acinar cells is required for the development of islets and for beta cell function during aging |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Exocrine-to-endocrine crosstalk in the pancreas is crucial to maintain beta cell function. However, the molecular mechanisms underlying this crosstalk are largely undefined. Trefoil factor 2 (Tff2) is a secreted factor known to promote the proliferation of beta cells in vitro, but its physiological role in vivo in the pancreas is unknown. Also, it remains unclear which pancreatic cell type expresses Tff2 protein. We therefore created a mouse model with a conditional knockout of Tff2 in the murine pancreas. We find that the Tff2 protein is preferentially expressed in acinar but not ductal or endocrine cells. Tff2 deficiency in the pancreas reduces beta cell mass on embryonic day 16.5. However, homozygous mutant mice are born without a reduction of beta cells and with acinar Tff3 compensation by day 7. When mice are aged to 1 year, both male and female homozygous and male heterozygous mutants develop impaired glucose tolerance without affected insulin sensitivity. Perifusion analysis reveals that the second phase of glucose-stimulated insulin secretion from islets is reduced in aged homozygous mutant compared to controls. Collectively, these results demonstrate a previously unknown role of Tff2 as an exocrine acinar cell-derived protein required for maintaining functional endocrine beta cells in mice.
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| Overall design |
Bulk mRNA-sequencing results of murine embryonic day 16.5 pancreatic tissue from control (Tff2fl/fl) versus conditional Tff2 KO (Pdx1:Cre;Tff2fl/fl) samples were compared and analyzed. In addition, bulk mRNA-sequencing results of isolated islets from 1-year-old control (Tff2fl/fl) versus conditional Tff2 KO (Pdx1:Cre;Tff2fl/fl) samples were compared and analyzed.
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| Contributor(s) |
Ortiz JA, Chen M, Wu X, Ku HT |
| Citation missing |
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| Submission date |
May 08, 2024 |
| Last update date |
May 13, 2024 |
| Contact name |
Steven T Rosen |
| Organization name |
City of Hope
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| Department |
Department of Hematology and Hematopoietic Cell Transplantation
|
| Street address |
1500 E. Duarte Road
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| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (16)
|
| GSM8258831 |
Embryonic Day 16.5 Pancreas - Pan 02 control |
| GSM8258832 |
Embryonic Day 16.5 Pancreas - Pan 08 control |
| GSM8258833 |
Embryonic Day 16.5 Pancreas - Pan 13 control |
| GSM8258834 |
Embryonic Day 16.5 Pancreas - Pan 01 knockout |
| GSM8258835 |
Embryonic Day 16.5 Pancreas - Pan 18 knockout |
| GSM8258836 |
Embryonic Day 16.5 Pancreas - Pan 19 knockout |
| GSM8258837 |
One-year-old Islets - Islet 052 control |
| GSM8258838 |
One-year-old Islets - Islet 826 control |
| GSM8258839 |
One-year-old Islets - Islet 829 control |
| GSM8258840 |
One-year-old Islets - Islet 857 control |
| GSM8258841 |
One-year-old Islets - Islet 858 control |
| GSM8258842 |
One-year-old Islets - Islet 055 knockout |
| GSM8258843 |
One-year-old Islets - Islet 122 knockout |
| GSM8258844 |
One-year-old Islets - Islet 803 knockout |
| GSM8258845 |
One-year-old Islets - Islet 812 knockout |
| GSM8258846 |
One-year-old Islets - Islet 845 knockout |
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| Relations |
| BioProject |
PRJNA1109385 |
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