# No Cell Left Behind:  Using Embryoid Bodies to Understand Human Biology

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2023 · $164,000

## Abstract

Abstract
This is a revised R21 proposal submitted in response to funding opportunity announcement PA-18-867, “Novel
Approaches for Relating Genetic Variation to Function and Disease”.
Most of the genetic variants that are associated with disease lie within non-coding DNA and are thought to
affect gene regulation. This has inspired efforts to identify variants that affect gene expression levels (eQTLs)
in a wide range of adult tissues. However, most disease-associated SNPs – though they are located in
putatively regulatory regions – have not been found to be eQTLs. One reason for this could be that despite
large-scale efforts to map eQTLs in diverse sets of tissues (e.g, GTEx), we still have not yet examined gene
regulation in the cell types or states most relevant for disease. Many human tissues and cell types, especially
those that are present in early development, are inaccessible due to practical or ethical constraints. Thus, the
pace of genetic discovery is fundamentally limited by access to relevant human tissues.
The discovery that mature human cells can be transformed into stem cells was an important step toward
solving this problem. Induced pluripotent stem cells (iPSCs) provide a renewable source of human tissue that
can, in theory, develop into any cell type. In practice, however, it can take years to discover how to produce
any single tissue from iPSCs using directed differentiation.
At the nexus of stem cell biology and emerging single-cell technologies, there is an opportunity to generate and
study many, or even most, human cell types simultaneously, all within a single dish. When grown in the proper
conditions, stem cells form spontaneously differentiating organoids known as embryoid bodies (EBs). Cells
within EBs differentiate asynchronously into cell types originating from all three germ layers, including
pluripotent, intermediate, and mature cell types. By applying single-cell RNA-sequencing (scRNA-seq) to cells
within EBs, we can jointly identify eQTLs across a multitude of cell types, all within a controlled genetic
environment. The use of EBs will also allow us to observe cellular transitions and regulatory events that are not
evident in static cell culture.

## Key facts

- **NIH application ID:** 10651667
- **Project number:** 5R21HG011170-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Yoav Gilad
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $164,000
- **Award type:** 5
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10651667

## Citation

> US National Institutes of Health, RePORTER application 10651667, No Cell Left Behind:  Using Embryoid Bodies to Understand Human Biology (5R21HG011170-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10651667. Licensed CC0.

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