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Functional, metabol...
Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
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Balboa, Diego (author)
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Barsby, Tom (author)
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Lithovius, Väinö (author)
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Saarimäki-Vire, Jonna (author)
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- Omar-Hmeadi, Muhmmad (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Dyachok, Oleg, 1965- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Montaser, Hossam (author)
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- Lund, Per-Eric (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Yang, Mingyu (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Ibrahim, Hazem (author)
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Näätänen, Anna (author)
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Chandra, Vikash (author)
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Vihinen, Helena (author)
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Jokitalo, Eija (author)
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Kvist, Jouni (author)
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Ustinov, Jarkko (author)
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Nieminen, Anni I (author)
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Kuuluvainen, Emilia (author)
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Hietakangas, Ville (author)
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- Katajisto, Pekka (author)
- Karolinska Institutet
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- Lau, Joey, 1979- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Carlsson, Per-Ola (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Barg, Sebastian, 1969- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Tengholm, Anders, 1971- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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Otonkoski, Timo (author)
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(creator_code:org_t)
- 2022-03-03
- 2022
- English.
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In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 40:7, s. 1042-1055
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Balboa, Diego
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Barsby, Tom
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Lithovius, Väinö
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Saarimäki-Vire, ...
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Omar-Hmeadi, Muh ...
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Dyachok, Oleg, 1 ...
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show more...
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Montaser, Hossam
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Lund, Per-Eric
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Yang, Mingyu
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Ibrahim, Hazem
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Näätänen, Anna
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Chandra, Vikash
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Vihinen, Helena
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Jokitalo, Eija
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Kvist, Jouni
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Ustinov, Jarkko
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Nieminen, Anni I
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Kuuluvainen, Emi ...
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Hietakangas, Vil ...
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Katajisto, Pekka
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Lau, Joey, 1979-
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Carlsson, Per-Ol ...
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Barg, Sebastian, ...
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Tengholm, Anders ...
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Otonkoski, Timo
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Biotechno ...
- By the university
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Uppsala University
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Karolinska Institutet