Hnf1b-CreER causes efficient recombination of a Rosa26-RFP reporter in duct and islet δ cells

The Hnf1b-CreERT2 BAC transgenic (Tg(Hnf1b-cre/ERT2)1Jfer) has been used extensively to trace the progeny of pancreatic ducts in developmental, regeneration, or cancer models. Hnf1b-CreERT2 transgenics have been used to show that the cells that form the embryonic pancreas duct-like plexus are bipote...

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Detalles Bibliográficos
Autores: Rovira, Meritxell, Martin, Miguel Ángel, Grau, Vanessa, Ferrer, Jorge
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/179424
Acceso en línea:https://hdl.handle.net/2445/179424
Access Level:acceso abierto
Palabra clave:Càncer de pàncrees
Regeneració (Biologia)
Cèl·lules
Pancreas cancer
Regeneration (Biology)
Cells
Descripción
Sumario:The Hnf1b-CreERT2 BAC transgenic (Tg(Hnf1b-cre/ERT2)1Jfer) has been used extensively to trace the progeny of pancreatic ducts in developmental, regeneration, or cancer models. Hnf1b-CreERT2 transgenics have been used to show that the cells that form the embryonic pancreas duct-like plexus are bipotent duct-endocrine progenitors, whereas adult mouse duct cells are not a common source of β cells in various regenerative settings. The interpretation of such genetic lineage tracing studies is critically dependent on a correct understanding of the cell type specificity of recombinase activity with each reporter system. We have reexamined the performance of Hnf1b-CreERT2 with a Rosa26-RFP reporter transgene. This showed inducible recombination of up to 96% adult duct cells, a much higher efficiency than previously used reporter transgenes. Despite this high duct-cell excision, recombination in α and β cells remained very low, similar to previously used reporters. However, nearly half of somatostatin-expressing δ cells showed reporter activation, which was due to Cre expression in δ cells rather than to duct to δ cell conversions. The high recombination efficiency in duct cells indicates that the Hnf1b-CreERT2 model can be useful for both ductal fate mapping and genetic inactivation studies. The recombination in δ cells does not modify the interpretation of studies that failed to show duct conversions to other cell types, but needs to be considered if this model is used in studies that aim to modify the plasticity of pancreatic duct cells.