# Patch-based deep scRNA-Seq to understand axon repair in the mammalian spinal cord

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $494,186

## Abstract

PROJECT SUMMARY / ABSTRACT
Traumatic spinal cord injury is a devastating condition that affect about 302,000 people in the United States, with
18,000 new cases each year. The limited ability of axons to regenerate after injury in the adult central nervous
system (CNS) underlies the permanent functional deficits and paralysis experienced by people with spinal cord
injury. Much research remains to be done to fully understand how regeneration is controlled by molecular and
cellular machinery in the neurons. This proposal builds on our recent success of applying Patch-based single
cell RNA sequencing technology to interrogate the molecular mechanism of corticospinal axon regeneration after
spinal cord injury. By sequencing only hundreds of neurons but at unusually high depths, we developed a
regeneration classifier that can be broadly applied to predict the regenerative potential of diverse neuronal types
based on their single cell profiles, the first of its kind in regenerative biology. Furthermore, this study implicates
key components in mitochondrial biogenesis and antioxidant response in regulating regeneration. Here we
propose to expand Patch-seq based single cell RNA sequencing approach in several ways. First, we will refine
and extend the regeneration classifier by sequencing additional corticospinal neurons and other neuronal types
with different regenerative capabilities. This will allow us to develop a more accurate regeneration classifier and
understand its full range of capabilities and limitations. Second, we will investigate the role of antioxidant
response and mitochondrial biogenesis with a comprehensive array of genetic gain and loss of function analyses
on NFE2L2 and PPARGC1A, master regulators of the two biological processes and two top candidates from our
Patch-seq study. Third, we will conduct deep sequencing on young versus old neurons to understand the age
impact on axon regeneration, which would be required to develop therapies that are robust across age groups.
Together, the proposed experiments using this unique deep single cell RNA sequencing approach will bring a
greater understanding of the neuron intrinsic control of axon regeneration, providing the foundation for
therapeutic development to promote repair and recovery after spinal cord injury.

## Key facts

- **NIH application ID:** 10999657
- **Project number:** 1R01NS139527-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Binhai Zheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $494,186
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999657

## Citation

> US National Institutes of Health, RePORTER application 10999657, Patch-based deep scRNA-Seq to understand axon repair in the mammalian spinal cord (1R01NS139527-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10999657. Licensed CC0.

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