| Title: |
Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis |
| Authors: |
Chong Gao, Qinghua Shi, Xue Pan, Jiajia Chen, Yuhong Zhang, Jiali Lang, Shan Wen, Xiaodong Liu, Tian-Lin Cheng, Kai Lei |
| Source: |
Cell Reports, Vol 43, Iss 3, Pp 113892- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CP: Neuroscience, Biology (General), QH301-705.5 |
| More Details: |
Summary: Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Due to the lack of trunk neuromuscular organoids (NMOs) from ALS patients’ induced pluripotent stem cells (iPSCs), an organoid system was missing to model the trunk spinal neuromuscular neurodegeneration. With the C9orf72 ALS patient-derived iPSCs and isogenic controls, we used an NMO system containing trunk spinal cord neural and peripheral muscular tissues to show that the ALS NMOs could model peripheral defects in ALS, including contraction weakness, neural denervation, and loss of Schwann cells. The neurons and astrocytes in ALS NMOs manifested the RNA foci and dipeptide repeat proteins. Acute treatment with the unfolded protein response inhibitor GSK2606414 increased the glutamatergic muscular contraction 2-fold and reduced the dipeptide repeat protein aggregation and autophagy. This study provides an organoid system for spinal neuromuscular pathologies in ALS and its application for drug testing. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2211124724002201; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2024.113892 |
| Access URL: |
https://doaj.org/article/d5afd73e42e94dc1903123b4edaf126b |
| Accession Number: |
edsdoj.5afd73e42e94dc1903123b4edaf126b |
| Database: |
Directory of Open Access Journals |
