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Series GSE117454 Query DataSets for GSE117454
Status Public on Dec 13, 2018
Title Diabetes Remission Using Glucose-Responsive Insulin-Producing Human α-Cells
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
Overall design Transcriptomic profiles of human pancreatic α-cells that convert into insulin-producing cells were generated by deep sequencing using Illumina Hi-seq 4000
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 Jul 20, 2018
Last update date Mar 21, 2019
Contact name Kenichiro Furuyama
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
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (39)
GSM3295672 sorted α-cells_1 [1_S1]
GSM3295673 sorted α-cells_2 [2_S2]
GSM3295675 sorted α-cells_3 [3_S3]
BioProject PRJNA482144
SRA SRP154584

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Supplementary file Size Download File type/resource
GSE117454_RNA_seq_matrix.txt.gz 1.2 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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