PT  - JOURNAL ARTICLE
AU  - Archana Yadav
AU  - Kaya J.E. Matson
AU  - Li Li
AU  - Isabelle Hua
AU  - Pallavi Gaur
AU  - Mor R. Alkaslasi
AU  - Saadia Hasan
AU  - Ahmad Galuta
AU  - Annemarie Dedek
AU  - Sara Ameri
AU  - Jessica Parnell
AU  - Mohammad M. Alshardan
AU  - Feras Abbas Qumqumji
AU  - Saud M. Alhamad
AU  - Alick Pingbei Wang
AU  - Gaetan Poulen
AU  - Nicolas Lonjon
AU  - Florence Vachiery-Lahaye
AU  - Mike A. Nalls
AU  - Yue A. Qi
AU  - Michael E. Hildebrand
AU  - Pierre-Francois Mery
AU  - Emmanuel Bourinet
AU  - Luc Bauchet
AU  - Eve C. Tsai
AU  - Michael E. Ward
AU  - Claire E. Le Pichon
AU  - Vilas Menon
AU  - Ariel J. Levine
TI  - The Human Motoneuron Expression Signature is Defined by ALS-Related Genes
AID  - 10.1101/2022.03.25.485808
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.25.485808
4099  - http://biorxiv.org/content/early/2022/03/28/2022.03.25.485808.short
4100  - http://biorxiv.org/content/early/2022/03/28/2022.03.25.485808.full
AB  - In neurodegenerative diseases of the human spinal cord, such as amyotrophic lateral sclerosis (ALS), motoneurons are particularly vulnerable to degeneration. It is hypothesized that their large size contributes to disease susceptibility, but the link between genetic variants associated with disease and cell-type specific degeneration is not clear. We characterized human spinal cord cells using single-nucleus RNA-sequencing and protein profiling. We found that human motoneurons displayed a unique expression profile characterized by factors involved in cytoskeletal structure, cell size, and degenerative disease (including ALS-associated genes SOD1, NEFH, OPTN, TUBA4A, PRPH, and STMN2) and that protein expression of these genes correlated with larger cell size in tissue. This work suggests a motoneuron-specific signature underlies their selective vulnerability to neurodegeneration.One-Sentence Summary Human spinal motoneurons preferentially express ALS genes, providing an explanation for their selective vulnerability to degeneration.Competing Interest StatementMichael A Nalls participation in this project was part of a competitive contract awarded to Data Tecnica International LLC by the National Institutes of Health to support open science research, he also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23 Inc.