The proposed project focuses on using human pluripotent stem cells (hPSCs) to generate advanced 3D organoid models to study the development and disease of the human neuromuscular system. The project aims to achieve three major objectives:
1. Generation of Position Specific (GPS) Organoids: Creating precise 3D models of human trunk development by instructing neuromesodermal progenitors (NMPs) to generate position-specific neuromuscular organoids (NMOs). This will enable the study of spinal cord neurons with precise positional identities and their coordinated development with corresponding muscles.
2. Study of Neuromuscular Diseases using NMOs: Utilizing the developed NMOs to model and study early and late-onset neuromuscular diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), to understand disease progression and identify potential drug targets.
3. Reconstruction of Human Corticospinal Tracts: Creating a 3D human in vitro model to study the formation and disruption of corticospinal tracts, which are essential for voluntary movements and often affected in neurological disorders, particularly ALS.
The project addresses the challenge of accurately modeling human neuromuscular development and diseases in vitro, particularly the lack of reliable models that incorporate the interactions between neural and muscle cells. Previous models have often focused on neuronal components in isolation, missing crucial cell types involved in the development of neuromuscular diseases. This project aims to overcome these limitations by developing comprehensive neuromuscular organoids that mirror human trunk development and pathology.
Importance for Society:
Understanding the mechanisms underlying neuromuscular development and diseases is critical for developing effective therapies and drugs. By generating 3D organoids that mimic the human neuromuscular system, this project provides a platform to study disease progression, identify potential drug candidates, and ultimately improve treatments for debilitating neuromuscular disorders, benefiting individuals and society as a whole.
