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| Status |
Public on Dec 15, 2018 |
| Title |
Diabetes Remission Using Glucose-Responsive Insulin-Producing Human alpha-Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Natural and stable cell identity switches, where terminally-differentiated cells convert into different cell-types when stressed, represent a widespread regenerative strategy in animals, yet they are poorly documented in mammals. In mice, some glucagon-producing pancreatic α-cells become insulin expressers upon ablation of insulin-secreting β-cells, promoting diabetes recovery. Whether human islets also display this plasticity for reconstituting β-like cells, especially in diabetic conditions, remains unknown. Here we show that two different islet non-β-cell types, α- and γ–cells, obtained from deceased non-diabetic or diabetic human donors can be lineage-traced and induced to produce insulin and secrete it in response to glucose. When transplanted into diabetic mice, converted human α-cells reverse diabetes and remain producing insulin even after 6 months. Insulin-producing α-cells maintain α-cell markers, as seen by deep transcriptomic and proteomic characterization, and display hypo-immunogenic features when exposed to T-cells derived from diabetic patients. These observations provide conceptual evidence and a molecular framework for a mechanistic understanding of in situ cell plasticity in islet cells, as well as in other organs, as a therapy for degenerative diseases by fostering the highly-regulated intrinsic cell regeneration.
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| Overall design |
Single-cell transcriptomic profiles of human pancreatic ?-cells that convert into insulin-producing cells were generated by deep sequencing using Illumina Hi-seq 4000.
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| Contributor(s) |
Furuyama K, Herrera PL |
| Citation(s) |
30760930 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| UC4 DK104209 |
Beta-cell Regeneration by Islet Cell Type Interconversion: Exploiting Islet Cell Plasticity for Diabetes Recovery |
University of Geneva |
PEDRO L HERRERA |
|
| Submission date |
Dec 14, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Kenichiro Furuyama |
| E-mail(s) |
kenichiro.furuyama@unige.ch
|
| Phone |
+41 22 379 5223
|
| Organization name |
University of Geneva
|
| Department |
Genetic Medicine and Development
|
| Lab |
Pedro Herrera
|
| Street address |
1, rue Michel-Servet
|
| City |
Geneva |
| State/province |
Geneva |
| ZIP/Postal code |
CH1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA510034 |
| SRA |
SRP173474 |
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