Bastidas-Ponce, A. ; Tritschler, S. ; Dony, L. ; Scheibner, K. ; Tarquis-Medina, M. ; Salinno, C. ; Schirge, S. ; Burtscher, I. ; Böttcher, A. ; Theis, F.J. ; Lickert, H. ; Bakhti, M.
Comprehensive single cell mRNA profiling reveals a detailed roadmap for pancreatic endocrinogenesis.
Development 146:dev173849 (2019)
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
Typ der Hochschulschrift
Herausgeber
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2019
Prepublished im Jahr
HGF-Berichtsjahr
2019
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 146,
Heft: 12,
Seiten: ,
Artikelnummer: dev173849
Supplement: ,
Reihe
Verlag
Company of Biologists
Verlagsort
Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30201 - Metabolic Health
30205 - Bioengineering and Digital Health
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP-Element(e)
G-502300-001
G-503800-001
G-501900-231
Förderungen
Copyright
Erfassungsdatum
2019-06-06