Acinar cells in the neonatal pancreas grow by self-duplication and not by neogenesis from duct cells

Onderzoeksoutput: Meeting abstract (Book)

Samenvatting

Acinar cells in the neonatal pancreas grow by self-duplication and not by neogenesis from duct cells Isabelle Houbracken1 and Luc Bouwens1 1Cell Differentiation Lab, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium Background and aims: Pancreatic acinar cells secrete digestive enzymes necessary for nutrient digestion in the intestine. They are considered the initiating cell type of pancreatic cancer and are endowed with differentiation plasticity that has been harnessed to regenerate endocrine beta cells. However, there is still uncertainty about the mechanisms of acinar cell formation during the dynamic period of early postnatal development. Materials and Methods: To unravel cellular contributions in the exocrine acinar development we studied two reporter mouse strains to trace the fate of acinar and duct cells during the first 4 weeks of life: ElastaseCreER R26-Lox-STOP-Lox-YFP and Hnf1bCreER R26-LacZ mice. Pups received tamoxifen on the day of birth and were followed during the next four weeks. Results: In the acinar reporter mice ElastaseCreER R26-YFP, the labelling index of acinar cells remained unchanged during the neonatal pancreas growth period (35.3 ± 5.4% YFP+ acinar cells (n = 7) at 1-week of age vs 35.4 ± 5.6% YFP+ acinar cells at week 4 (n = 10) (p > 0.05)), evidencing that acinar cells are formed by self-duplication. In line with this, duct cell tracing in Hnf1bCreER R26-LacZ mice did not show significant increase in acinar cell labelling (0.02 ± 0.02% X-gal+ acinar cells at 4-weeks of age (n = 4)), excluding duct-to-acinar cell contribution during neonatal development. Immunohistochemical analysis confirms massive levels of acinar cell proliferation in this early period of life, as more than 40% of amylase+ cells are positive for Ki67 at week 1. Further, also increase in acinar cell size contributes to the growth of pancreatic mass (48-80 % increase between 1- and 4-weeks of age in TAM and non-TAM-treated animals, respectively). Moreover, the mean number of acinar nuclei per acinus remains constant throughout neonatal development. Conclusion: We conclude that the growth of acinar cells during physiological neonatal pancreas development is by self-duplication (and hypertrophy) rather than neogenesis from progenitor cells as was suggested before. Grant acknowledgement: FWO project and research fellowship, VUB: price Ignace Vanderschueren 2012
Originele taal-2English
Titeloral presentation Post-EASD workshop "The Beta Cell in Health, Disease and after Therapy"
Pagina'sO16-O16
Aantal pagina's1
StatusPublished - 6 okt 2018
EvenementPost-EASD workshop 2018 "The Beta Cell in Health, Disease and after Therapy" - Potsdam, Germany
Duur: 5 okt 20187 okt 2018

Conference

ConferencePost-EASD workshop 2018 "The Beta Cell in Health, Disease and after Therapy"
LandGermany
StadPotsdam
Periode5/10/187/10/18

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