Generation of human islet cell type-specific identity genesets

Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics m...

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Vydáno v:Nature communications Ročník 13; číslo 1; s. 2020 - 14
Hlavní autoři: van Gurp, Léon, Fodoulian, Leon, Oropeza, Daniel, Furuyama, Kenichiro, Bru-Tari, Eva, Vu, Anh Nguyet, Kaddis, John S., Rodríguez, Iván, Thorel, Fabrizio, Herrera, Pedro L.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 19.04.2022
Nature Publishing Group
Nature Portfolio
Témata:
13/106
13/31
38
38/32
38/91
631/337/2019
692/53/2423
692/699/2743/137
Beta cells
Cell differentiation
Cell Differentiation - genetics
Cell therapy
Diabetes
Diabetes mellitus
Differentiation (biology)
Embryogenesis
Humanities and Social Sciences
Humans
Insulin
Insulin - genetics
Insulin-Secreting Cells
Islets of Langerhans
Meta-analysis
multidisciplinary
Pluripotency
Pluripotent Stem Cells
Science
Science (multidisciplinary)
Stem cells
Transcriptomics
ISSN:2041-1723, 2041-1723
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Shrnutí:Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells. These genesets define islet cellular identities better than previously published genesets. We show their efficacy to outline cell identity changes and unravel some of their underlying genetic mechanisms, whether during embryonic pancreas development or in experimental setups aiming at developing glucose-responsive insulin-secreting cells, such as pluripotent stem-cell differentiation or in adult islet cell reprogramming protocols. These islet cell type-specific genesets represent valuable tools that accurately benchmark gain and loss in islet cell identity traits. Cell therapy to replace β-cells is a potential therapeutic avenue to treat diabetes, but the production of insulin-secreting replacement cells requires reliable tools to assess islet cellular identity. Here the authors use single-cell transcriptomics meta-analysis to construct gene sets that describe the identity of human α-, β-, γ- and δ-cells.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-29588-8