# Aging dependent transformation of oligodendrocyte precursor cells

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $335,688

## Abstract

Summary:
To sustain neural signaling and enable plasticity throughout life, the nervous system relies on homeostatic
interactions with a diverse population of glial cells, which create and modify the extracellular matrix, remove
ions and neurotransmitters, provide metabolic support and promote functional reorganization of circuits in
response to changing patterns of activity. Although most studies of glial cells have focused on the three main
classes of glia – astrocytes, oligodendrocytes and microglia – the mammalian brain also contains an abundant,
highly dynamic population of glial progenitors termed oligodendrocyte precursor cells (OPCs or NG2 glia).
These lineage restricted progenitors play crucial roles in generating oligodendrocytes to enable production of
new myelin sheaths during motor learning and replacement of myelin destroyed through disease, such as
multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). OPCs remain widely distributed in gray and
white matter throughout life, but exhibit profound changes in behavior with aging, including reduced
proliferation and differentiation. Emerging evidence suggests that OPCs do more than serve as progenitors for
oligodendrocytes, as they are found in regions where there is no myelin, and like microglia, OPCs migrate to
sites of injury and contribute to scar formation, features unrelated to their role in oligodendrogenesis and
myelin repair. OPCs share many other features with microglia – they are present at a similar density, maintain
a grid-like distribution, possess ramified, radially-oriented processes and are highly dynamic, continuously
exploring their surrounding environment with motile filopodia. Moreover, recent evidence indicates that OPCs
can transform into inflammatory OPCs (iOPCs) that engulf and present exogenous antigens through MHC
class I and II when exposed to inflammatory cytokines, suggesting that they may modulate tissue inflammation.
While microglia and astrocytes are known to undergo phenotypic changes in response to inflammation that
profoundly influence the aging brain, much less is known about the role of OPCs in this context, despite their
persistence in brain circuits. In part, this lack of knowledge stems from the limited molecular and physiological
interrogation of OPCs that has been completed in vivo. OPCs are underrepresented in available single cell
RNA-seq datasets and there have been no studies specifically designed to define how changes in their
properties with aging are influenced by their prior behavior. We will leverage a diverse array of methodologies
and our combined expertise in physiology, molecular and computational biology to define the causes and
consequences of age-dependent changes in these ubiquitous glial cells. The new insight provided by these
studies may lead to a deeper understanding of the homeostatic roles performed by these glial cells, and reveal
new approaches for rejuvenating their regenerative potential to sustain brain fun...

## Key facts

- **NIH application ID:** 10833020
- **Project number:** 5R01AG072305-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** DWIGHT E BERGLES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $335,688
- **Award type:** 5
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833020

## Citation

> US National Institutes of Health, RePORTER application 10833020, Aging dependent transformation of oligodendrocyte precursor cells (5R01AG072305-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10833020. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*