Combinatorial transcription factor profiles predict mature and functional human islet α and β cells
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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-09-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.151621 |
| _version_ | 1811329170842583040 |
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| author | Shristi Shrestha Diane C. Saunders John T. Walker Joan Camunas-Soler Xiao-Qing Dai Rachana Haliyur Radhika Aramandla Greg Poffenberger Nripesh Prasad Rita Bottino Roland Stein Jean-Philippe Cartailler Stephen C.J. Parker Patrick E. MacDonald Shawn E. Levy Alvin C. Powers Marcela Brissova |
| author_facet | Shristi Shrestha Diane C. Saunders John T. Walker Joan Camunas-Soler Xiao-Qing Dai Rachana Haliyur Radhika Aramandla Greg Poffenberger Nripesh Prasad Rita Bottino Roland Stein Jean-Philippe Cartailler Stephen C.J. Parker Patrick E. MacDonald Shawn E. Levy Alvin C. Powers Marcela Brissova |
| author_sort | Shristi Shrestha |
| collection | DOAJ |
| description | 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 more than 40,000 cells from normal human islets by single-cell RNA-Seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells coexpressing 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-coexpressing β cells showed enhanced electrophysiological activity. Thus, these results indicate that combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations. |
| first_indexed | 2024-04-13T15:39:05Z |
| format | Article |
| id | doaj.art-a176612b370447eeb2aad97352fda235 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T15:39:05Z |
| publishDate | 2021-09-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-a176612b370447eeb2aad97352fda2352022-12-22T02:41:12ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-09-01618Combinatorial transcription factor profiles predict mature and functional human islet α and β cellsShristi ShresthaDiane C. SaundersJohn T. WalkerJoan Camunas-SolerXiao-Qing DaiRachana HaliyurRadhika AramandlaGreg PoffenbergerNripesh PrasadRita BottinoRoland SteinJean-Philippe CartaillerStephen C.J. ParkerPatrick E. MacDonaldShawn E. LevyAlvin C. PowersMarcela BrissovaIslet-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 more than 40,000 cells from normal human islets by single-cell RNA-Seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells coexpressing 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-coexpressing β cells showed enhanced electrophysiological activity. Thus, these results indicate that combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.https://doi.org/10.1172/jci.insight.151621Cell biologyEndocrinology |
| spellingShingle | Shristi Shrestha Diane C. Saunders John T. Walker Joan Camunas-Soler Xiao-Qing Dai Rachana Haliyur Radhika Aramandla Greg Poffenberger Nripesh Prasad Rita Bottino Roland Stein Jean-Philippe Cartailler Stephen C.J. Parker Patrick E. MacDonald Shawn E. Levy Alvin C. Powers Marcela Brissova Combinatorial transcription factor profiles predict mature and functional human islet α and β cells JCI Insight Cell biology Endocrinology |
| title | Combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| title_full | Combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| title_fullStr | Combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| title_full_unstemmed | Combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| title_short | Combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| title_sort | combinatorial transcription factor profiles predict mature and functional human islet α and β cells |
| topic | Cell biology Endocrinology |
| url | https://doi.org/10.1172/jci.insight.151621 |
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