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Project

Single-Cell Transcriptome and Epigenome of Regenerating CST Neurons

Funder: Craig H Neilsen Foundation

Funding period
USD 150 K
Funding amount
Abstract
Spinal cord injury (SCI) is a severe condition that results in loss of function in mobility. The corticospinal tract (CST) is a clinically important target for functional recovery after SCI. Multiple molecular pathways including the Pten/mTOR signaling pathway have been revealed to promote axon regeneration and sprouting from the CST. However, among diverse populations of CST neurons, only subsets of them regenerate axons following molecular intervention. Better understanding of the heterogeneity within corticospinal motor neurons is much needed. Here, we propose to characterize the regenerating corticospinal motor neurons using cutting-edge single cell technologies, In Aim 1, we propose to apply single cell patch-seq pipeline on regenerating and non-regenerating population of neurons to understand the transcriptomic changes regulating the axon regeneration. In Aim 2, we propose to study the epigenetic regulations behind the regeneration using single cell ATAC-seq. In Aim 3, we propose to test the function of the Aim 1 and 2 identified genes and regulatory elements for axon regeneration in vivo using the mouse model of SCI. Our proposed study will provide novel knowledge on genetic and epigenetic regulation of the regeneration of corticospinal motor neurons that control voluntary movement. This study will also allow us to understand why only a subset of corticospinal motor neurons regenerates while others do not. With the expertise on spinal cord regeneration in Dr. Zheng’s lab, this proposed Neilsen fellowship will allow me to develop this project to fruition, which will have an impact in the field. The support from the Neilsen fellowship will also propel me to launch an independent research career to fight paralysis caused by SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    0604 Genetics

  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Human Genome

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Spinal Cord Injury

  • RCDC

    Genetics

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    1.1 Normal biological development and functioning

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science