Główne pojęcia
Treponema pallidum infection inhibits the differentiation of neural progenitor cell subcluster 1B, reducing the number of hindbrain neurons and affecting the neurodevelopment of brain organoids.
Streszczenie
The study used single-cell RNA sequencing (scRNA-seq) to analyze the effects of Treponema pallidum (T. pallidum) infection on the development of brain organoids derived from induced pluripotent stem cells (iPSCs).
Key findings:
- T. pallidum infection reduced the overall size of brain organoids and disrupted the formation of neural rosette-like structures.
- scRNA-seq analysis revealed that T. pallidum infection decreased the proportion of neural progenitor cells (NPCs) and neurons in the organoids.
- Specifically, T. pallidum inhibited the differentiation of the subNPC1B subcluster, leading to a reduction in the number of hindbrain neurons.
- The transcription factor TCF3 and the notch signaling pathway were identified as potential mediators of the inhibitory effects of T. pallidum on the subNPC1B-hindbrain neuron differentiation axis.
- These findings provide insights into the pathogenesis of congenital neurodevelopmental impairment associated with T. pallidum infection and suggest that the brain organoid model can be a useful platform for studying the impact of congenital infections on human brain development.
Statystyki
The size of T. pallidum-infected brain organoids was significantly smaller than the control group (P<0.01).
The expressions of endodermal markers Ve-cad, KDR, and SOX17 were significantly upregulated in the T. pallidum group (P < 0.05), while the expressions of ectodermal genes MAP2, Nestin, and SOX2 were significantly decreased (P < 0.05).
The proportion of neural progenitor cell (NPC)1, NPC2 and neuron population were 12.5%, 1.72%, and 9.1%, respectively, following T. pallidum infection (P < 0.05).
The proportion of the CD71-/CD49b- neuron population in the T. pallidum group was significantly lower than the control group (P < 0.01).
The expressions of hindbrain neuron markers MAGEH1, MEIS3 and USP47 were significantly decreased following T. pallidum infection (P<0.05–0.01).
Cytaty
"T. pallidum infection influenced the formation of neural rosette structures and affected the neurodevelopment of the brain organoid."
"T. pallidum reduced the cell number of subNPC1B subclusters and affected brain organoid development."
"T. pallidum inhibited the differentiation of hindbrain neurons in the brain organoids."