# Craniofacial skeletal cell lineage plasticity for reconstituting stem cells and their niches

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $411,163

## Abstract

PROJECT SUMMARY/ABSTRACT
The craniofacial skeletal tissues are composed of multiple functional units, encompassing both mineralized and
non-mineralized components. The non-mineralized tissues, such as sutures, cranial base synchondroses and
periodontal ligaments, exist between mineralized tissues, and play important roles in craniofacial growth and
regeneration by providing a niche for tissue-specific stem cells in postnatal life. Current cell-based therapies
cannot effectively reconstitute stem cell niches; as a result, recovery of devastating skeletal conditions such as
craniofacial deformities and advanced alveolar bone loss associated with periodontal diseases has not been
made possible to date. Functional regeneration of craniofacial skeletal tissues requires an innovative approach
to reestablish inherent stem cells and their supporting niches. In this proposal, we aim to define molecular and
cellular mechanisms underlying developmental plasticity of the craniofacial skeletal lineage and explore the
possibility to apply these mechanisms to enhance endogenous regeneration capacity. We hypothesize that
functionally dedicated cells of the postnatal craniofacial skeletal cell lineage can reconstitute tissue-specific
stem cells and their supporting niches through lineage plasticity. We will test this hypothesis using a
combination of in vivo clonal lineage-tracing and single-cell and spatial transcriptomic approaches to unravel
fundamental molecular and cellular events associated with formation of stem cells and their stem cell niche.
We will focus on two models of the cranial base synchondrosis and the periodontium to investigate
developmental craniofacial skeletal lineage plasticity. In Aim 1, we will characterize plasticity of Runx2+
perichondrial cells in establishing the cranial base synchondrosis niche. We hypothesize Runx2+ perichondrial
fibroblasts generate both stem cells and their niches within postnatal synchondroses through developmental
plasticity. We will use a combination of cell-lineage tracing experiments and single-cell transcriptomic analyses,
high-resolution spatial transcriptomic analysis and CRISPR screens using the feature barcoding technology to
define molecular mechanisms underlying developmental plasticity and stem cell-generating potential of Runx2+
perichondrial cells of the postnatal synchondrosis. In Aim 2, we will explore the possibility to reactivate PTHrP+
cementoblasts to regenerate functional periodontal attachment apparatus. We hypothesize that PTHrP+
cementoblasts on the adult root surface retain a dental follicle (DF) cell-like state, and can be experimentally
reverted to dental root mesenchymal progenitor cells. We will use a combination of cell-lineage tracing
experiments, single-cell and bulk transcriptomic and epigenomic analyses to define how PTHrP+
cementoblasts are related to PTHrP+ DF cells, and change their molecular identities during periodontal
destruction and regeneration. We will also examine whe...

## Key facts

- **NIH application ID:** 10792479
- **Project number:** 5R01DE030630-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Noriaki Ono
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,163
- **Award type:** 5
- **Project period:** 2022-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792479

## Citation

> US National Institutes of Health, RePORTER application 10792479, Craniofacial skeletal cell lineage plasticity for reconstituting stem cells and their niches (5R01DE030630-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10792479. Licensed CC0.

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