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| Status |
Public on Sep 09, 2021 |
| Title |
Combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled >40,000 cells from normal human islets by scRNA-seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells co-expressing ARX/MAFB (α cells) and MAFA/MAFB (β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-seq, MAFA/MAFB co-expressing β cells showed enhanced electrophysiological activity. Thus, these results indicate combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.
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| Overall design |
Single cell RNAseq data of human pancreatic islets from 5 non-diabetic donors. 2 out of the 5 donors also include single cell RNAseq data from FAC-sorted alpha and beta cells. 1 out of the total 5 donors also include bulk rnaseq data.
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| Contributor(s) |
Brissova M, Powers AC |
| Citation(s) |
34428183 |
| Submission date |
Sep 07, 2021 |
| Last update date |
Oct 13, 2021 |
| Contact name |
Marcela Brissova |
| E-mail(s) |
marcela.brissova@Vanderbilt.edu
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| Organization name |
Vanderbilt University Medical Center
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| Street address |
1211 Medical Center Dr
|
| City |
Nashville |
| State/province |
TN |
| ZIP/Postal code |
37232 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA761336 |
| SRA |
SRP335985 |
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