# Development of iPSCs for comparative genomics in primates

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2024 · $559,888

## Abstract

Abstract
This is a competitive renewal application for a second term of this project (years 5-8).
Characterizing gene regulatory differences between humans and our close primate relatives is essential for
understanding the molecular basis of human-specific traits. Comparative genomics provides us with the tools to
identify both species-specific and conserved regulatory features, which has provided valuable insight into the genetic
architecture of adaptation in gene regulation. However, ethical and practical considerations preclude comparative
studies of molecular traits in live primates, particularly apes. Frozen post-mortem tissues from non-human apes are
difficult to obtain, and even when they are available, they are not optimal templates for many functional genomic
assays. Thus, we are generally unable to collect samples from enough individuals to map and study gene regulatory
loci in non-human apes; we are unable to study gene regulation in more than a few tissues from apes; we are unable
to study the dynamics of gene regulation during development; and we are unable to study regulatory responses to
evolutionarily and clinically relevant exposures.
In the first term of this project, we proposed to address this challenge by establishing a comparative panel of induced
pluripotent stem cells (iPSCs) from humans and chimpanzees. We have successfully done this, and we have shared
these lines freely and without restriction with more than 30 labs (see letters of support), facilitating comparative
functional genomic studies by investigators who would not otherwise have been able to obtain appropriate samples
to conduct their research. We now request support to continue to maintain and distribute this community resource,
which we will expand in two ways. First, we will generate additional chimpanzee iPSC lines using the remaining
samples we collected prior to the moratorium on chimpanzee research. We expect that these lines will soon become
the only population-sample resource for future studies involving chimpanzees in the USA. Second, we will use
human and chimpanzee iPSCs to develop a series of dynamically differentiating organoids, which we will also share
freely to allow other groups to effectively utilize the comparative iPSC panel. The unique property of these
dynamically differentiating organoids is that they contain asynchronously differentiating cells. While they do not
produce pure cell populations that can be meaningfully analyzed with bulk RNA-seq data, single-cell RNA-seq can
be used to deconvolve the organoids into dozens of cell types and developmental stages, allowing us to explore
dynamic regulatory processes that cannot be observed in adult tissues10.

## Key facts

- **NIH application ID:** 10879097
- **Project number:** 5R01HG010772-06
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Yoav Gilad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $559,888
- **Award type:** 5
- **Project period:** 2019-09-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879097

## Citation

> US National Institutes of Health, RePORTER application 10879097, Development of iPSCs for comparative genomics in primates (5R01HG010772-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10879097. Licensed CC0.

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