Abstract：
:Cell-identity switches, in which terminally differentiated cells are converted 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 and somatostatin-producing δ-cells become insulin-expressing cells after the ablation of insulin-secreting β-cells, thus promoting diabetes recovery. Whether human islets also display this plasticity, especially in diabetic conditions, remains unknown. Here we show that islet non-β-cells, namely α-cells and pancreatic polypeptide (PPY)-producing γ-cells, obtained from deceased non-diabetic or diabetic human donors, can be lineage-traced and reprogrammed by the transcription factors PDX1 and MAFA to produce and secrete insulin in response to glucose. When transplanted into diabetic mice, converted human α-cells reverse diabetes and continue to produce insulin even after six months. Notably, insulin-producing α-cells maintain expression of α-cell markers, as seen by deep transcriptomic and proteomic characterization. These observations provide conceptual evidence and a molecular framework for a mechanistic understanding of in situ cell plasticity as a treatment for diabetes and other degenerative diseases.
journal_name
Naturejournal_title
Natureauthors
Furuyama K,Chera S,van Gurp L,Oropeza D,Ghila L,Damond N,Vethe H,Paulo JA,Joosten AM,Berney T,Bosco D,Dorrell C,Grompe M,Ræder H,Roep BO,Thorel F,Herrera PLdoi
10.1038/s41586-019-0942-8subject
Has Abstractpub_date
2019-03-01 00:00:00pages
43-48issue
7746eissn
0028-0836issn
1476-4687pii
10.1038/s41586-019-0942-8journal_volume
567pub_type
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