Characterization of CD90/Thy-1 as a crucial molecular signature for myogenic differentiation in human urine-derived cells through single-cell RNA sequencing.
Sci Rep
; 14(1): 2329, 2024 01 28.
Article
in En
| MEDLINE
| ID: mdl-38282008
ABSTRACT
Human urine-derived cells (UDCs) are primary cultured cells originating from the upper urinary tract and are known to be multipotent. We previously developed MYOD1-transduced UDCs (MYOD1-UDCs) as a model recapitulating the pathogenesis of Duchenne muscular dystrophy (DMD) caused by a lack of dystrophin. MYOD1-UDCs also allow evaluation of the efficacy of exon skipping with antisense oligonucleotides. However, despite the introduction of MYOD1, some MYOD1-UDCs failed to form myotubes, possibly because of heterogeneity among UDCs. Here, we carried out single-cell RNA-sequencing analyses and revealed that CD90/Thy-1 was highly expressed in a limited subpopulation of UDCs with high myogenic potency. Furthermore, CD90-positive MYOD1-UDCs, but not CD90-negative cells, could form myotubes expressing high levels of myosin heavy chain and dystrophin. Notably, overexpression of CD90 in CD90-negative MYOD1-UDCs did not enhance myogenic differentiation, whereas CD90 suppression in CD90-positive UDCs led to decreased myotube formation and decreased myosin heavy chain expression. CD90 may thus contribute to the fusion of single-nucleated MYOD1-UDCs into myotubes but is not crucial for promoting the expression of late muscle regulatory factors. Finally, we confirmed that CD90-positive MYOD1-UDCs derived from patients with DMD were a valuable tool for obtaining a highly reproducible and stable evaluation of exon skipping using antisense oligonucleotide.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dystrophin
/
Muscular Dystrophy, Duchenne
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2024
Document type:
Article
Affiliation country:
Japón