Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord-Like Organoid (pSCO) with Dorsoventral Organization

Kyubin Seo, Subin Cho, Hyogeun Shin, Aeri Shin, Ju Hyun Lee, June Hoan Kim, Boram Lee, Hwanseok Jang, Youngju Kim, Hyo Min Cho, Yongdoo Park, Hee Youn Kim, Taeseob Lee, Woong Yang Park, Yong Jun Kim, Esther Yang, Dongho Geum, Hyun Kim, Il Joo Cho, Sanghyuk LeeJae Ryun Ryu, Woong Sun

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Axis formation and related spatial patterning are initiated by symmetry breaking during development. A geometrically confined culture of human pluripotent stem cells (hPSCs) mimics symmetry breaking and cell patterning. Using this, polarized spinal cord organoids (pSCOs) with a self-organized dorsoventral (DV) organization are generated. The application of caudalization signals promoted regionalized cell differentiation along the radial axis and protrusion morphogenesis in confined hPSC colonies. These detached colonies grew into extended spinal cord-like organoids, which established self-ordered DV patterning along the long axis through the spontaneous expression of polarized DV patterning morphogens. The proportions of dorsal/ventral domains in the pSCOs can be controlled by the changes in the initial size of micropatterns, which altered the ratio of center-edge cells in 2D. In mature pSCOs, highly synchronized neural activity is separately detected in the dorsal and ventral side, indicating functional as well as structural patterning established in the organoids. This study provides a simple and precisely controllable method to generate spatially ordered organoids for the understanding of the biological principles of cell patterning and axis formation during neural development.

Original languageEnglish
Article number2301787
JournalAdvanced Science
Volume10
Issue number20
DOIs
Publication statusPublished - 2023 Jul 18

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords

  • dorsoventral organization
  • human pluripotent stem cells
  • microcontact printing
  • spinal cord organoid
  • symmetry breaking

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Chemical Engineering
  • General Materials Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Engineering
  • General Physics and Astronomy

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