# Reconstructing positional information in the eye from scRNA-seq and relating it to signal transduction

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2022 · $184,547

## Abstract

PROJECT SUMMARY
This proposal is a new application entitled "Reconstructing positional information in the eye from scRNA-seq
and relating it to signal transduction".
The question of how cell fates are accurately specified is of fundamental importance to understanding both
normal developmental progression and disease mechanisms that alter cell fates. However we currently have
very limited understanding of how gene expression is coordinated across time and space in a multicellular
tissue so that cells accurately and reproducibly negotiate the transition from a multipotent to a differentiated
state. Single-cell RNA sequencing (scRNA-seq) promises to describe each cell in a tissue in terms of a state,
defined as the global pattern of mRNA expression inside the cell. Cells are dissociated from a tissue and are
subject to individual sequencing. A major limitation is the difficulty in reconstructing the spatial position of each
sequenced cell in the tissue. The goal of this proposal is to develop a radically new method to acheive
accurate spatial mapping of scRNA-seq data, thereby inferring the number and configuration of cell states. The
method relies on physical principles to mathematically order the data onto a 2D lattice that simulates the
tissue. In our case, the relevant tissue is the developing retina. The Drosophila retina provides a superbly
tractable and well-defined experimental model with which to address this problem. In particular, the
stereotyped patterning and architecture of the retina facilitates the identification and tracking of individual cell
types over space and time. Therefore, we have a rigorous “ground truth” to which to judge our method, refining
it and modifying it to attain optimal and accurate mapping of scRNA-seq data onto spatial coordinates of a
tissue. Our method could help expand the use of scRNA-seq to discover new cell types and their positions in
less characterized tissues and organs, including the mammalian eye.
Aim 1 will generate scRNA-seq data, and the quantitative datasets will be used to construct a spatial model
that integrates information about cell states across both time and space.
Aim 2 will investigate how specific features of cell-cell signaling contribute to the positioning of cell
differentiation in the developing eye. Because signaling mechanisms have proven to be extraordinarily
conserved, our exploration of the signaling interactions that drive differentiation are likely to be relevant to
mammalian development and disease.

## Key facts

- **NIH application ID:** 10318197
- **Project number:** 5R21EY032233-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Richard W. CARTHEW
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $184,547
- **Award type:** 5
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318197

## Citation

> US National Institutes of Health, RePORTER application 10318197, Reconstructing positional information in the eye from scRNA-seq and relating it to signal transduction (5R21EY032233-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10318197. Licensed CC0.

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