Willmann, S. ; Müller, N.S. ; Engert, S. ; Sterr, M. ; Burtscher, I. ; Raducanu, A. ; Irmler, M. ; Beckers, J. ; Sass, S. ; Theis, F.J. ; Lickert, H.
The global gene expression profile of the secondary transition during pancreatic development.
Mech. Dev. 139, 51-64 (2016)
Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF+ pancreatic epithelium from the FVF− surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5–15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with the mRNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation.
Impact Factor
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Times Cited
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Altmetric
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Ductal ; Endocrine ; Exocrine ; Foxa2 ; Organogenesis ; Pancreas; Beta-cell; Organ Formation; Islet; Differentiation; Endocrine; Mouse; Organogenesis; Morphogenesis; Foxa2; Association
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2016
Prepublished im Jahr
2015
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
0925-4773
e-ISSN
1872-6356
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 139,
Heft: ,
Seiten: 51-64
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
Amsterdam
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
30502 - Diabetes: Pathophysiology, Prevention and Therapy
Forschungsfeld(er)
Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e)
G-502300-001
G-503800-001
G-501900-231
G-500600-004
G-500600-005
G-500600-006
G-501900-064
Förderungen
Copyright
Erfassungsdatum
2015-12-02