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Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model

Author

Listed:
  • Haley Masters

    (University of California Irvine
    University of California Irvine)

  • Shuxiong Wang

    (University of California Irvine)

  • Christina Tu

    (University of California Irvine)

  • Quy Nguyen

    (University of California Irvine)

  • Yutong Sha

    (University of California Irvine
    University of California Irvine)

  • Matthew K. Karikomi

    (University of California Irvine)

  • Pamela Shi Ru Fung

    (University of California Irvine)

  • Benjamin Tran

    (University of California Irvine)

  • Cristina Martel

    (University of California Irvine)

  • Nellie Kwang

    (University of California Irvine)

  • Michael Neel

    (University of California Irvine)

  • Olga G. Jaime

    (University of California Irvine)

  • Victoria Espericueta

    (University of California Irvine)

  • Brett A. Johnson

    (University of California Irvine)

  • Kai Kessenbrock

    (University of California Irvine)

  • Qing Nie

    (University of California Irvine
    University of California Irvine)

  • Edwin S. Monuki

    (University of California Irvine
    University of California Irvine
    University of California Irvine)

Abstract

Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) display canonical properties and dynamic motile multiciliated phenotypes that interact with Aβ uptake. Single dCPEC transcriptomes over time correlate well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlight the direct CPEC origin from neuroepithelial cells. In addition, time series analyses define metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contract. These temporal patterns are then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest dynamic models of ChP support for the developing human brain.

Suggested Citation

  • Haley Masters & Shuxiong Wang & Christina Tu & Quy Nguyen & Yutong Sha & Matthew K. Karikomi & Pamela Shi Ru Fung & Benjamin Tran & Cristina Martel & Nellie Kwang & Michael Neel & Olga G. Jaime & Vict, 2025. "Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60361-9
    DOI: 10.1038/s41467-025-60361-9
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