# Dissecting the interplay of gene regulatory networks and cellular niche on cell fate determination

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $310,000

## Abstract

A single totipotent zygote has the remarkable ability to give rise to an entire multi-cellular organism.
Methodologies to comprehensively map and modulate the parameters that govern this transformation will have
far ranging impact on our understanding of development and also our ability to restore normal function in
damaged or diseased tissues. While these processes have typically been studied in the context of model
organisms, the advent of human pluripotent stem cells (hPSCs) has opened a powerful paradigm to
recapitulate human development in ex vivo settings. Indeed hPSCs have been successfully differentiated to
most somatic cell types of interest and recently also into complex three-dimensional organoids. These
differentiation systems are beginning to offer an unprecedented insight into human biology, however two
fundamental challenges have persisted: one, enabling efficacious differentiation of hPSCs to a mature
phenotype that recapitulates an adult versus an embryonic or fetal tissue-of-origin like state; and two,
generation of scalable and architecturally reproducible organotypic tissues. Focusing on liver differentiation
from hPSCs, in this proposal we will explore the hypothesis that these two key objectives are intertwined, and
achieving a mature phenotype is potentially linked to the establishment of an appropriate cellular niche.
Towards this we will develop an integrated genome engineering and tissue engineering approach that will
allow systematic manipulation of both genetic and cellular microenvironmental parameters during hPSC
differentiation. Using this framework we hope to enable a deeper understanding of the interplay of gene
regulatory networks and cellular niche on cell fate determination; and also potentially guide development of
methodologies towards programming the processes of organogenesis for regenerative medicine applications.

## Key facts

- **NIH application ID:** 10146416
- **Project number:** 5R01GM123313-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Prashant Mali
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $310,000
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146416

## Citation

> US National Institutes of Health, RePORTER application 10146416, Dissecting the interplay of gene regulatory networks and cellular niche on cell fate determination (5R01GM123313-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10146416. Licensed CC0.

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