# Thyroid Follicular Cell Signaling and Development in Humans

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $371,131

## Abstract

Project Summary
The development of the thyroid gland from anterior endoderm is an essential step in development that allows for
the production of thyroid hormones around week 12 in utero in humans. Unfortunately, in about 1/4000 births
genetic mutations that affect this development pathway lead to congenital hypothyroidism requiring lifelong
thyroid hormone replacement therapy. Thus, a better understanding of thyroid follicular cell development could
lead to a process where genetic editing and cellular therapy could provide treatment for congenital
hypothyroidism (CH). Our work in this area has utilized a directed differentiation approach and has identified
bone morphogenic protein and fibroblast growth factor as key mediators of thyroid follicular cell lineage
development across species resulting in functional murine thyroid follicular cells that can rescue athyreotic mice.
In this proposal, we now turn our attention exclusively to human thyroid follicular cell development and propose
three Specific Aims that will allow for the pre-clinical development of functioning human thyroid follicular cells
derived from human induced pluripotent stem cells (iPSCs), In the first Aim we will utilize a novel lineage tracing
methodology to understand how developing human thyroid follicular acquire their cell fate and to ensure that the
process in iPSC parallels that in vivo. In the second Aim we will prove that the human thyroid follicular cells
derived from iPSCs are fully able to produce thyroid hormones in vitro and can be transplanted into
immunodeficient athyreotic mice to rescue their hypothyroidism. Finally, in the third Aim we will demonstrate pre-
clinically that derived iPSCs from a patient with CH can be genetically corrected and re-introduced via transplant
to function normally. Together completion of these Aims will provide key insight into the possibilities of iPSC
derived cellular therapy for the treatment of CH and enhance our understanding of the development endodermal-
derived tissues in humans.

## Key facts

- **NIH application ID:** 10298043
- **Project number:** 2R01DK105029-06
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ANTHONY N HOLLENBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $371,131
- **Award type:** 2
- **Project period:** 2015-12-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10298043

## Citation

> US National Institutes of Health, RePORTER application 10298043, Thyroid Follicular Cell Signaling and Development in Humans (2R01DK105029-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10298043. Licensed CC0.

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