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Comprehensive single cell mRNA profiling reveals a detailed roadmap for pancreatic endocrinogenesis.

Development 146:dev173849 (2019)
Verlagsversion Postprint Forschungsdaten DOI
Open Access Green
Deciphering mechanisms of endocrine cell induction, specification and lineage allocation in vivo will provide valuable insights into how the islets of Langerhans are generated. Currently, it is ill defined how endocrine progenitors segregate into different endocrine subtypes during development. Here, we generated a novel neurogenin 3 (Ngn3)-Venus fusion (NVF) reporter mouse line, that closely mirrors the transient endogenous Ngn3 protein expression. To define an in vivo roadmap of endocrinogenesis, we performed single cell RNA sequencing of 36,351 pancreatic epithelial and NVF+ cells during secondary transition. This allowed Ngn3(low) endocrine progenitors, Ngn3(high) endocrine precursors, Fev(+) endocrine lineage and hormone(+) endocrine subtypes to be distinguished and time-resolved, and molecular programs during the step-wise lineage restriction steps to be delineated. Strikingly, we identified 58 novel signature genes that show the same transient expression dynamics as Ngn3 in the 7260 profiled Ngn3-expressing cells. The differential expression of these genes in endocrine precursors associated with their cell-fate allocation towards distinct endocrine cell types. Thus, the generation of an accurately regulated NVF reporter allowed us to temporally resolve endocrine lineage development to provide a fine-grained single cell molecular profile of endocrinogenesis in vivo.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Endocrine Progenitor-precursor ; Neurog3 ; Single Cell Rna Sequencing ; Endocrinogenesis ; Endocrine Cell Allocation ; Mouse; Endocrine Progenitors; Differentiation; Mouse; Neurogenin3; Organogenesis; Expression; Phosphorylation; Maintenance; Lineage; Plexus
ISSN (print) / ISBN 0950-1991
e-ISSN 1477-9129
Quellenangaben Band: 146, Heft: 12, Seiten: , Artikelnummer: dev173849 Supplement: ,
Verlag Company of Biologists
Verlagsort Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Begutachtungsstatus