TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration.
Acute pancreatitis
Embryonic development
Organ regeneration
Pancreatic development
TBX3
Journal
BMC biology
ISSN: 1741-7007
Titre abrégé: BMC Biol
Pays: England
ID NLM: 101190720
Informations de publication
Date de publication:
20 03 2023
20 03 2023
Historique:
received:
09
03
2022
accepted:
27
02
2023
entrez:
21
3
2023
pubmed:
22
3
2023
medline:
23
3
2023
Statut:
epublish
Résumé
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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 36941669
doi: 10.1186/s12915-023-01553-x
pii: 10.1186/s12915-023-01553-x
pmc: PMC10029195
doi:
Substances chimiques
T-Box Domain Proteins
0
TBX3 protein, human
0
Tbx3 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55Informations de copyright
© 2023. The Author(s).
Références
Biomed Pharmacother. 2020 Oct;130:110612
pubmed: 32771895
Dev Cell. 2020 Oct 26;55(2):150-162.e6
pubmed: 32857951
Development. 2005 Jul;132(13):3139-49
pubmed: 15944193
Stem Cell Reports. 2021 Nov 9;16(11):2617-2627
pubmed: 34653400
Development. 2018 Nov 26;145(23):
pubmed: 30478225
Adv Healthc Mater. 2022 Jun;11(11):e2102345
pubmed: 35114730
Int J Med Sci. 2013 Apr 17;10(6):738-46
pubmed: 23630438
Appl Biochem Biotechnol. 2009 Aug;158(2):253-61
pubmed: 18931944
Development. 2019 Apr 25;146(8):
pubmed: 30936179
Nat Metab. 2019 Feb;1(2):222-235
pubmed: 32694784
Cell. 2006 Nov 3;127(3):469-80
pubmed: 17081971
Dis Model Mech. 2012 Jul;5(4):503-14
pubmed: 22266944
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1490-5
pubmed: 15668393
STAR Protoc. 2022 Dec 16;3(4):101869
pubmed: 36595896
Wiley Interdiscip Rev Syst Biol Med. 2012 May-Jun;4(3):273-83
pubmed: 22334480
Am J Cancer Res. 2017 Jun 01;7(6):1389-1406
pubmed: 28670499
Stem Cell Reports. 2015 Dec 8;5(6):1155-1170
pubmed: 26651606
Development. 2018 Sep 3;145(17):
pubmed: 30042181
Stem Cells Dev. 2015 Aug 15;24(16):1833-51
pubmed: 25952667
Development. 2014 Oct;141(20):3819-33
pubmed: 25294936
Cell Rep. 2015 Sep 8;12(10):1594-605
pubmed: 26321631
Cell Syst. 2016 Oct 26;3(4):346-360.e4
pubmed: 27667365
Nat Genet. 2002 Sep;32(1):128-34
pubmed: 12185368
Gene. 2020 Feb 5;726:144223
pubmed: 31669645
Eur J Immunol. 2007 Jan;37(1):43-53
pubmed: 17171761
Genome Biol. 2014;15(12):550
pubmed: 25516281
PLoS Biol. 2011 Sep;9(9):e1001143
pubmed: 21909240
Cancers (Basel). 2021 Oct 13;13(20):
pubmed: 34680288
Nat Methods. 2016 Jul;13(7):577-80
pubmed: 27240256
Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18617-18626
pubmed: 32675240
Circ Res. 2008 Sep 26;103(7):743-50
pubmed: 18723448
Gastroenterology. 2009 May;136(5):1701-10
pubmed: 19208343
PLoS Genet. 2014 Mar 27;10(3):e1004247
pubmed: 24675841
Cell. 2021 Jun 24;184(13):3573-3587.e29
pubmed: 34062119
Development. 2002 May;129(10):2447-57
pubmed: 11973276
PLoS One. 2014 Oct 24;9(10):e110191
pubmed: 25343378
Nat Commun. 2021 May 25;12(1):3144
pubmed: 34035279
Nat Commun. 2015 Jul 29;6:7677
pubmed: 26220524
Mod Pathol. 2014 Oct;27(10):1355-63
pubmed: 24658583
Gastroenterology. 2008 Feb;134(2):544-55
pubmed: 18242220
Biostatistics. 2017 Apr 1;18(2):275-294
pubmed: 27756721
J Clin Invest. 2010 Feb;120(2):508-20
pubmed: 20071774
Proc Natl Acad Sci U S A. 1980 Jul;77(7):4113-7
pubmed: 6933460
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Elife. 2020 Jul 16;9:
pubmed: 32672536
Front Physiol. 2018 Feb 27;9:129
pubmed: 29535635
Biostatistics. 2018 Oct 1;19(4):562-578
pubmed: 29121214
Nat Genet. 2003 Jul;34(3):267-73
pubmed: 12808457
Stem Cells Int. 2016;2016:6759343
pubmed: 26697078
Annu Rev Physiol. 2015;77:229-49
pubmed: 25386992
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Biochim Biophys Acta Mol Cell Res. 2020 Mar;1867(3):118509
pubmed: 31306714
Biotechniques. 2012 May;52(5):332-4
pubmed: 22578126
Nat Methods. 2017 Apr;14(4):381-387
pubmed: 28263961
Dev Biol. 2008 Apr 1;316(1):74-86
pubmed: 18294628
Anat Embryol (Berl). 1997 May;195(5):419-25
pubmed: 9176664
Nat Commun. 2018 Sep 25;9(1):3922
pubmed: 30254276
Cell Mol Life Sci. 2012 Apr;69(8):1377-89
pubmed: 22130515
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Genes Dev. 2007 May 1;21(9):1098-112
pubmed: 17473172
BMC Bioinformatics. 2021 Jan 6;22(1):5
pubmed: 33407064
Dev Cell. 2016 Oct 24;39(2):239-253
pubmed: 27720610
Cancer Immunol Res. 2018 Nov;6(11):1388-1400
pubmed: 30266715
Nat Med. 1997 Jun;3(6):646-50
pubmed: 9176491
J Biol Chem. 2011 Mar 11;286(10):8425-8436
pubmed: 21189255
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Commun Biol. 2021 Nov 17;4(1):1298
pubmed: 34789845
Stem Cell Res. 2016 Sep;17(2):367-378
pubmed: 27632063
Development. 2003 May;130(10):2263-73
pubmed: 12668638
Genes Dev. 1995 Mar 15;9(6):700-13
pubmed: 7537238
Cancer Res. 2017 Oct 15;77(20):5576-5590
pubmed: 28790064
Nat Biomed Eng. 2021 Aug;5(8):897-913
pubmed: 34239116
STAR Protoc. 2021 Dec 08;2(4):100913
pubmed: 34917972
Nature. 2018 Oct;562(7727):367-372
pubmed: 30283141
Stem Cells Int. 2019 Jun 2;2019:8475389
pubmed: 31281387
Cell Stem Cell. 2021 Jun 3;28(6):1105-1124.e19
pubmed: 33915078
Elife. 2016 Apr 05;5:
pubmed: 27046536
Nat Rev Immunol. 2018 Jan;18(1):35-45
pubmed: 28787399
J Cell Biol. 2013 Aug 5;202(3):563-77
pubmed: 23918941
Adv Sci (Weinh). 2021 May 13;8(14):2100626
pubmed: 34306986
Nat Med. 2021 Nov;27(11):1928-1940
pubmed: 34663987
EMBO J. 2013 May 15;32(10):1393-408
pubmed: 23584530
Cells. 2022 Feb 08;11(3):
pubmed: 35159392
Proc Natl Acad Sci U S A. 2012 Jan 17;109(3):E154-63
pubmed: 22203979
J Anat. 2004 Jul;205(1):1-13
pubmed: 15255957
Gastroenterology. 2008 Aug;135(2):621-31
pubmed: 18515092
Nat Methods. 2014 Feb;11(2):163-6
pubmed: 24363023
Stem Cell Reports. 2013 Aug 29;1(3):248-65
pubmed: 24319661
Nat Biotechnol. 2015 May;33(5):495-502
pubmed: 25867923