
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.


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Congenital syphilis is a vertically transmitted bacterial infection caused by Treponema pallidum , often causing multidomain neurodevelopmental disabilities. However, little is known about the pathogenesis of this disease. Brain organoids platform derived from the induced pluripotent stem cell (iPSC) is employed and exposed to T. pallidum infection for modelling congenital neurodevelopmental impairment. Single-cell RNA sequencing is used for identifying the subpopulations of differentially expressed genes and cellular heterogeneity and reconstructing differentiation trajectories following T. pallidum infection. The results reveal that T. pallidum infection influences the formation of neural rosette structures, reduces the cell number of the neural progenitor cell subcluster 1B (subNPC1B) and hindbrain neurons, and affects the neurodevelopment of the brain organoid. Moreover, it is speculated that T. pallidum inhibit the hindbrain neuron cell number through the suppression of subNPC1B subgroup in the organoids and inhibits transcription factor 3 activity in the subNPC1B-hindbrain neuronal axis. This is the first report on the inhibited effects of T. pallidum on the neurodevelopment of the iPSC-derived brain organoid model. It is concluded that T. pallidum could inhibit the differentiation of subNPC1B in brain organoids, thereby reducing the differentiation from subNPC1B to hindbrain neurons, and ultimately affecting the development and maturation of hindbrain neurons.

### Competing Interest Statement

The authors have declared no competing interest.

Single-cell RNA sequencing of iPSC-derived brain organoids reveals Treponema pallidum infection inhibiting neurodevelopment

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Single-cell RNA sequencing reveals Treponema pallidum infection inhibits neurodevelopment in brain organoids
