# Dissecting Stem Cell Heterogeneity in the Zebrafish Skeletal System

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $46,836

## Abstract

PROJECT SUMMARY/ABSTRACT:
Skeletal tissues provide structure that allows movement and protects essential organs in the body from
damage. Whereas bone displays some capacity for repair, non-healing bone injuries remain a major financial
and medical burden. Understanding the potential for skeletal stem cells (SSCs) to improve bone repair
therefore holds great promise. A challenge for the field of craniofacial bone repair is that these bones have a
different developmental trajectory from the more studied limb bones and undergo direct ossification rather than
cartilage-mediated repair in response to injury. Thus, it remains unclear the extent to which the repair of
craniofacial intramembranous bones depends on the same suites of SSCs as those of the limbs. In this
proposal, I investigate a hypothesis that there are two fundamentally distinct origins of SSCs in bones: one
type of SSC derived from naïve mesenchymal cells in the embryonic perichondrium and periosteum (PO-
SSCs) and a second type derived from hypertrophic chondrocytes of the growth plate, which dedifferentiate
and move into the marrow cavity (GP-SSCs). Using intersectional genetics, lineage tracing, conditional cell
ablation, and assays of open chromatin, I will test that GP-SSCs are especially important for cartilage callus
formation due to maintenance of accessible cartilage enhancers from their growth plate origin (i.e. epigenetic
memory). In the craniofacial intramembranous bones, the lack of growth plates and hence GP-SSCs would
result in direct ossification during repair. To test these models, I have developed innovative models of
intramembranous (premaxilla) and endochondral (ceratohyal) bone regeneration in the adult zebrafish head.
Using parallel Cre-Lox and Dre-Lox systems, I will be able to simultaneously trace PO-SSCs and GP-SSCs
and assess their contributions to and requirements for the repair of intramembranous versus endochondral
bone repair. Together, my studies should reveal mechanisms by which SSCs regenerate intramembranous
bones differently than endochondral bones, which will inform approaches to specifically repair the
intramembranous bones of the face and skull. My mentor, Dr. Gage Crump, has an exceptional training record
and runs the Development, Stem Cells, and Regenerative Medicine program to which I belong. The Crump lab
is located within the rapidly growing Broad Stem Cell Institute, which is a highly collaborative and dynamic
environment for my scientific development. These interactions will help me in adapting emerging techniques
such as scRNAseq and ATACseq to my novel zebrafish bone regeneration models. A training plan that
incorporates acquisition of skillsets in zebrafish genetics and imaging, specialized coursework in genomics, the
honing of presentation and writing skills, and career development will help me in achieving my goal of
becoming a successful independent scientist in the field of craniofacial regenerative medicine.

## Key facts

- **NIH application ID:** 10179346
- **Project number:** 5F31DE029682-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Claire Elizabeth Arata
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,836
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179346

## Citation

> US National Institutes of Health, RePORTER application 10179346, Dissecting Stem Cell Heterogeneity in the Zebrafish Skeletal System (5F31DE029682-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10179346. Licensed CC0.

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