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Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells

2022· article· en· 414 citations· W4214950345 on OpenAlex· 10.1038/s41587-022-01219-z

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A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Opus teacher head0.013
GPT teacher head0.231
Teacher spread
0.218 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Transplantation of pancreatic islet cells derived from human pluripotent stem cells is a promising treatment for diabetes. Despite progress in the generation of stem-cell-derived islets (SC-islets), no detailed characterization of their functional properties has been conducted. Here, we generated functionally mature SC-islets using an optimized protocol and benchmarked them comprehensively against primary adult islets. Biphasic glucose-stimulated insulin secretion developed during in vitro maturation, associated with cytoarchitectural reorganization and the increasing presence of alpha cells. Electrophysiology, signaling and exocytosis of SC-islets were similar to those of adult islets. Glucose-responsive insulin secretion was achieved despite differences in glycolytic and mitochondrial glucose metabolism. Single-cell transcriptomics of SC-islets in vitro and throughout 6 months of engraftment in mice revealed a continuous maturation trajectory culminating in a transcriptional landscape closely resembling that of primary islets. Our thorough evaluation of SC-islet maturation highlights their advanced degree of functionality and supports their use in further efforts to understand and combat diabetes.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Nature Biotechnology
Topic
Pancreatic function and diabetes
Field
Medicine
Canadian institutions
Funders
Biocenter FinlandHelsinki Institute of Life Science, Helsingin YliopistoInnovative Medicines InitiativeVetenskapsrådetBarndiabetesfondenEuropean Federation of Pharmaceutical Industries and AssociationsNovo NordiskDiabetes Wellness Suomi SäätiöLeona M. and Harry B. Helmsley Charitable TrustNovo Nordisk FondenAcademy of FinlandStiftelsen Familjen Ernfors FondUniversity of AlbertaSigrid Juséliuksen Säätiö
Keywords
IsletPancreatic isletsBiologyCell biologyTransplantationTranscriptomeInduced pluripotent stem cellStem cellInsulinExocytosisSecretionInternal medicineEndocrinologyEmbryonic stem cellGeneBiochemistryGene expressionMedicine
Has abstract in OpenAlex
yes