Stage specific reprogramming of mouse embryo liver cells to a beta cell-like phenotype

Ying Yang, Ersin Akinci, James R. Dutton, Anannya Banga, Jonathan M W Slack

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

We show that cultures of mouse embryo liver generate insulin-positive cells when transduced with an adenoviral vector encoding the three genes: Pdx1, Ngn3 and MafA (Ad-PNM). Only a proportion of transduced cells become insulin-positive and the highest yield occurs in the period E14-16, declining at later stages. Insulin-positive cells do not divide further although they can persist for several weeks. RT-PCR analysis of their gene expression shows the upregulation of a whole battery of genes characteristic of beta cells including upregulation of the endogenous counterparts of the input genes. Other features, including a relatively low insulin content, the expression of genes for other pancreatic hormones, and the fact that insulin secretion is not glucose-sensitive, indicate that the insulin-positive cells remain immature. The origin of the insulin-positive cells is established both by co-immunostaining for α-fetoprotein and albumin, and by lineage tracing for Sox9, which is expressed in the ductal plate cells giving rise to biliary epithelium. This shows that the majority of insulin-positive cells arise from hepatoblasts with a minority from the ductal plate cells.

Original languageEnglish (US)
Pages (from-to)602-612
Number of pages11
JournalMechanisms of Development
Volume130
Issue number11-12
DOIs
StatePublished - Nov 2013

Bibliographical note

Funding Information:
We are grateful to Lucas Greder for assistance with adenovirus production. This work was supported by Grant R01DK080747 from the National Institutes of Health (NIDDK) .

Keywords

  • Beta cell
  • Hepatoblast
  • MafA
  • Ngn3
  • Pdx1
  • Sox9

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