Human Choroid Plexus Organoids Progress to Postnatal-like Maturation and Reveal a Closing Window of Developmental Plasticity
- 1King's College London
Abstract
The choroid plexus (ChP) produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier, yet the developmental programme driving its maturation in humans remains poorly understood. Using a 15-timepoint single-cell RNA sequencing atlas of human ChP organoids benchmarked against human tissue, we resolve an ordered differentiation process comprising cell cycle exit, ciliogenesis and ion transporter expression. Maturation culminates in a transcriptional state with features of human adult ChP, establishing the first in vitro ChP model to reach postnatal-like milestones. Centrosome proteomics identified previously uncharacterised, stage-specific regulators of ciliogenesis. To probe developmental plasticity, we perturbed ChP organoids with valproic acid (VPA), a clinically used antiepileptic and established teratogen. Early VPA-mediated disruption of multiciliogenesis and secretion recovered upon drug withdrawal, whereas late treatment washout resulted in persistent impairment of mature transporters. Together, these findings resolve the developmental programme by which the ChP reaches functionally mature identity and identify a stage-dependent plasticity window during its maturation.
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BibTeX
@misc{apsley2026human,
title = {{Human Choroid Plexus Organoids Progress to Postnatal-like Maturation and Reveal a Closing Window of Developmental Plasticity}},
author = {E. J. Apsley and S. S. Tang and E. Vitiello and I. Imaz-Rosshandler and M. Fernandez-Otero and K. Sapidou and S. A. Burnap and W. B. Struwe and M. Pjanic and J. F. Fullard and J. Bendl and P. Roussos and K. R. Long and F. Gergely and M. A. Lancaster and L. Pellegrini},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.12.758506},
url = {https://www.biorxiv.org/content/10.64898/2026.10.12.758506v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Human Choroid Plexus Organoids Progress to Postnatal-like Maturation and Reveal a Closing Window of Developmental Plasticity
AU - E. J. Apsley
AU - S. S. Tang
AU - E. Vitiello
AU - I. Imaz-Rosshandler
AU - M. Fernandez-Otero
AU - K. Sapidou
AU - S. A. Burnap
AU - W. B. Struwe
AU - M. Pjanic
AU - J. F. Fullard
AU - J. Bendl
AU - P. Roussos
AU - K. R. Long
AU - F. Gergely
AU - M. A. Lancaster
AU - L. Pellegrini
PY - 2026
DA - 2026/10/12
PB - bioRxiv
DO - 10.64898/2026.10.12.758506
UR - https://www.biorxiv.org/content/10.64898/2026.10.12.758506v1
AB - The choroid plexus (ChP) produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier, yet the developmental programme driving its maturation in humans remains poorly understood. Using a 15-timepoint single-cell RNA sequencing atlas of human ChP organoids benchmarked against human tissue, we resolve an ordered differentiation process comprising cell cycle exit, ciliogenesis and ion transporter expression. Maturation culminates in a transcriptional state with features of human adult ChP, establishing the first in vitro ChP model to reach postnatal-like milestones. Centrosome proteomics identified previously uncharacterised, stage-specific regulators of ciliogenesis. To probe developmental plasticity, we perturbed ChP organoids with valproic acid (VPA), a clinically used antiepileptic and established teratogen. Early VPA-mediated disruption of multiciliogenesis and secretion recovered upon drug withdrawal, whereas late treatment washout resulted in persistent impairment of mature transporters. Together, these findings resolve the developmental programme by which the ChP reaches functionally mature identity and identify a stage-dependent plasticity window during its maturation.
ER -