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Melzer, M.K.* ; Schirge, S. ; Gout, J.* ; Arnold, F.* ; Srinivasan, D.* ; Burtscher, I. ; Allgöwer, C.* ; Mulaw, M.* ; Zengerling, F.* ; Günes, C.* ; Lickert, H. ; Christoffels, V.M.* ; Liebau, S.* ; Wagner, M.* ; Seufferlein, T.* ; Bolenz, C.* ; Moon, A.M.* ; Perkhofer, L.* ; Kleger, A.*

TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration.

BMC Biol. 21:55 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: The reactivation of genetic programs from early development is a common mechanism for injury-induced organ regeneration. T-box 3 (TBX3) is a member of the T-box family of transcription factors previously shown to regulate pluripotency and subsequent lineage commitment in a number of tissues, including limb and lung. TBX3 is also involved in lung and heart organogenesis. Here, we provide a comprehensive and thorough characterization of TBX3 and its role during pancreatic organogenesis and regeneration. RESULTS: We interrogated the level and cell specificity of TBX3 in the developing and adult pancreas at mRNA and protein levels at multiple developmental stages in mouse and human pancreas. We employed conditional mutagenesis to determine its role in murine pancreatic development and in regeneration after the induction of acute pancreatitis. We found that Tbx3 is dynamically expressed in the pancreatic mesenchyme and epithelium. While Tbx3 is expressed in the developing pancreas, its absence is likely compensated by other factors after ablation from either the mesenchymal or epithelial compartments. In an adult model of acute pancreatitis, we found that a lack of Tbx3 resulted in increased proliferation and fibrosis as well as an enhanced inflammatory gene programs, indicating that Tbx3 has a role in tissue homeostasis and regeneration. CONCLUSIONS: TBX3 demonstrates dynamic expression patterns in the pancreas. Although TBX3 is dispensable for proper pancreatic development, its absence leads to altered organ regeneration after induction of acute pancreatitis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acute Pancreatitis ; Embryonic Development ; Organ Regeneration ; Pancreatic Development ; Tbx3; Gene-expression; Mammary-gland; Stem-cells; Lef1; Rna; Program; Catenin; Lineage; Protein; Cancer
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
e-ISSN 1741-7007
Zeitschrift BMC Biology
Quellenangaben Band: 21, Heft: 1, Seiten: , Artikelnummer: 55 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Regeneration Research (IDR)
Institute of Stem Cell Research (ISF)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
30204 - Cell Programming and Repair
Forschungsfeld(er) Helmholtz Diabetes Center
Stem Cell and Neuroscience
PSP-Element(e) G-501900-231
G-502300-001
G-500800-001
Förderungen German Center for Diabetes Research (DZD)
Helmholtz Association
DFG
German Cancer Aid
Deutsche Forschungsgemeinschaft (DFG) "Sachbeihilfe"
Projekt DEAL
DOI 10.1186/s12915-023-01553-x
WOS ID 000953812700004
Scopus ID 85150752228
PubMed ID 36941669
Erfassungsdatum 2023-10-06
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