# Annotated lineage trees of murine development

> **NIH NIH DP2** · DARTMOUTH COLLEGE · 2022 · $1,476,000

## Abstract

Understanding the forces that direct cell fate is a central goal of biology. Many fundamental questions remain
unanswered and vast tracts of vertebrate development are almost completely unexplored. What are the
developmental origins and lineage relationships of cell types? What, where, and when are the key molecular
events that underlie cell fate transitions? These questions remain unanswered as we lack the technology to
map cell fate in both high-throughput and high-resolution. The overall objective of the proposed work is to
develop and apply novel technologies that track and translate the cell fate forces into human-decipherable
recordings. Our proposal combines innovative use of new CRISPR systems, molecular recording technologies,
and improvements to our established lineage tracing technology to reconstruct high accuracy, annotated
lineage trees. We will apply these cell fate technologies in mouse embryonic stem cells (mESCs), where we
will track differentiation into various progeny cells, generating both transcriptional and lineage maps describing
the probabilistic relationship between intestinal cell types at high-resolution. We will then expand these
systems into recording mouse lines, where both molecular and lineage recordings can be captured from
terminally differentiated cells. In aggregate, the resulting high-resolution lineage maps and tools will provide
new insight into the plasticity of cell fate, and these recording mouse lines will be a valuable resource to the
biomedical community. We believe these trailblazing technologies will ultimately spur the development of novel
fate modulators with application to human disease.

## Key facts

- **NIH application ID:** 10472805
- **Project number:** 1DP2GM149750-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Aaron H McKenna
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,476,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472805

## Citation

> US National Institutes of Health, RePORTER application 10472805, Annotated lineage trees of murine development (1DP2GM149750-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10472805. Licensed CC0.

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