# The Role of GATA3 and SATB2 in Early Colonic Patterning

> **NIH NIH R56** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $377,500

## Abstract

The hindgut gives rise to colorectal and urothelial/bladder fates. The generation of these 2
fates requires the partitioning of the hindgut. Improper partitioning of the hindgut causes
anorectal malformations. We have generated a powerful new in vitro model that allows for the
generation of both colorectal and urothelial organoids from human induced pluripotent stem
cells (IPSCs) through the transient activation of Bone Morphogenetic Protein (BMP) signaling.
Using this in vitro model, we’ve identified WNT signaling as a critical extrinsic signal that
specifies urothelial progenitors and represses colorectal progenitors. In addition, using
CRISPR-Cas9 mediated editing of human IPSCs, we found that urothelial specification is
perturbed in GATA3 deficient cells. Based on these observations we formulated the
hypothesis that two developmental pathways, BMP and WNT, converge to induce
expression of GATA3 which subsequently represses CDX2 in urothelial progenitors.
This hypothesis will be tested in 2 specific aims:
Aim 1: Determine the mechanism of cooperative BMP and WNT signaling in the
activation of GATA3 in the urothelium .
Aim 2: Determine the molecular mechanisms through which CDX2 is repressed in the
urothelium.
Using our in vitro model of colorectal and urothelial differentiation, we will determine how BMP
and WNT signaling converge to induce expression of GATA3. In addition, we will determine if
GATA3 drives urothelial specification through the inhibition of CDX2. These studies will
elucidate key mechanisms of hindgut partitioning which will enable the development of
improved colonic and urothelial organoids which can be used for disease modeling and for
organ replacement.

## Key facts

- **NIH application ID:** 10665389
- **Project number:** 1R56DK129575-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** JORGE O MUNERA
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,500
- **Award type:** 1
- **Project period:** 2022-09-16 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10665389

## Citation

> US National Institutes of Health, RePORTER application 10665389, The Role of GATA3 and SATB2 in Early Colonic Patterning (1R56DK129575-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10665389. Licensed CC0.

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