# Molecular Basis of Human Hepatic Progenitor Cell Formation

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $423,391

## Abstract

Project Summary
In the previous funding cycle, we examined the mechanism through which FGF and BMP
specify the endoderm to adopt a hepatic fate. We revealed that FGF has a critical role in
controlling expression of a WNT inhibitor called NKD1. NKD1 transiently suppresses WNT
activity, which is needed to promote hepatic fate. BMP controls hepatic fate through activation of
SMAD1. This signaling pathway regulates expression of several developmental regulators. Like
FGF, BMP induces NKD1. BMP also controls expression of several regulators of chromatin
structure including TFAP2A and ARID5B. In the current proposal, we will study the roles of
TFAP2A and ARID5B in generating hepatic progenitor cells. We had also had previously shown
that GATA6 is necessary for hepatic specification in mouse embryos. We, therefore, propose to
determine the mechanism through which GATA6 controls hepatic fate. We hypothesize that
GATA6 acts as a pioneer transcription factor to promote the competency of the endoderm to
respond to inductive cues.

## Key facts

- **NIH application ID:** 10434825
- **Project number:** 5R01DK102716-09
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** STEPHEN A DUNCAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,391
- **Award type:** 5
- **Project period:** 2014-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434825

## Citation

> US National Institutes of Health, RePORTER application 10434825, Molecular Basis of Human Hepatic Progenitor Cell Formation (5R01DK102716-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434825. Licensed CC0.

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