TitleCD34 Identifies a Subset of Proliferating Microglial Cells Associated with Degenerating Motor Neurons in ALS.
Publication TypeJournal Article
Year of Publication2019
AuthorsKovacs M, Trias E, Varela V, Ibarburu S, Beckman JS, Moura IC, Hermine O, King PH, Si Y, Kwon Y, Barbeito L
JournalInt J Mol Sci
Date Published2019 Aug 09
KeywordsAmyotrophic Lateral Sclerosis, Animals, Antigens, CD34, Cell Proliferation, Cells, Cultured, Humans, Male, Microglia, Motor Neurons, Point Mutation, Protein Folding, Rats, Spinal Cord, Superoxide Dismutase-1

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons accompanied by proliferation of reactive microglia in affected regions. However, it is unknown whether the hematopoietic marker CD34 can identify a subpopulation of proliferating microglial cells in the ALS degenerating spinal cord. Immunohistochemistry for CD34 and microglia markers was performed in lumbar spinal cords of ALS rats bearing the SOD1 mutation and autopsied ALS and control human subjects. Characterization of CD34-positive cells was also performed in primary cell cultures of the rat spinal cords. CD34 was expressed in a large number of cells that closely interacted with degenerating lumbar spinal cord motor neurons in symptomatic SOD1 rats, but not in controls. Most CD34 cells co-expressed the myeloid marker CD11b, while only a subpopulation was stained for Iba1 or CD68. Notably, CD34 cells actively proliferated and formed clusters adjacent to damaged motor neurons bearing misfolded SOD1. CD34 cells were identified in the proximity of motor neurons in autopsied spinal cord from sporadic ALS subjects but not in controls. Cell culture of symptomatic SOD1 rat spinal cords yielded a large number of CD34 cells exclusively in the non-adherent phase, which generated microglia after successive passaging. A yet unrecognized CD34 cells, expressing or not the microglial marker Iba1, proliferate and accumulate adjacent to degenerating spinal motor neurons, representing an intriguing cell target for approaching ALS pathogenesis and therapeutics.

Alternate JournalInt J Mol Sci
PubMed ID31395804
PubMed Central IDPMC6720880
Grant List- / / Sistema Nacional de Investigadores (SNI) /
R01 NS092651 / NS / NINDS NIH HHS / United States
- / / Programa de Desarrollo de las Ciencias Básicas (PEDECIBA) /
00482 / / Amyotrophic Lateral Sclerosis Association /
COF 03/11 / / Institut Pasteur de Montevideo-FOCEM /
- / / Agencia Nacional de Investigación e Innovación /
#1104 / / Comisión Sectorial de Investigación Científica (CSIC), Universidad de la República, Uruguay; Grupos I+D Program /