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Functional, metabol...
Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells.
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-03-03
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Springer Nature,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-473728
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-473728URI
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https://doi.org/10.1038/s41587-022-01219-zDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:149272207URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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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, MuhmmadUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)muhhm810
(author)
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Dyachok, Oleg,1965-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)olegdyac
(author)
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Montaser, Hossam
(author)
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Lund, Per-EricUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)peerlund
(author)
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Yang, MingyuUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)minya266
(author)
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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, PekkaKarolinska Institutet
(author)
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Lau, Joey,1979-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)jolau226
(author)
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Carlsson, Per-OlaUppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)perocarl
(author)
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Barg, Sebastian,1969-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)sebba507
(author)
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Tengholm, Anders,1971-Uppsala universitet,Institutionen för medicinsk cellbiologi(Swepub:uu)andeteng
(author)
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Otonkoski, Timo
(author)
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Uppsala universitetInstitutionen för medicinsk cellbiologi
(creator_code:org_t)
Related titles
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In:Nature Biotechnology: Springer Nature40:7, s. 1042-10551087-01561546-1696
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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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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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MEDICAL AND HEAL ...
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Uppsala University
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Karolinska Institutet