TY - JOUR
KW - dorsoventral organization
KW - human pluripotent stem cells
KW - microcontact printing
KW - spinal cord organoid
KW - symmetry breaking
AU - Kyubin Seo
AU - Subin Cho
AU - Hyogeun Shin
AU - Aeri Shin
AU - Ju-Hyun Lee
AU - June Hoan Kim
AU - Boram Lee
AU - Hwanseok Jang
AU - Youngju Kim
AU - Hyo Min Cho
AU - Yongdoo Park
AU - Hee Youn Kim
AU - Taeseob Lee
AU - Woong-Yang Park
AU - Yong Jun Kim
AU - Esther Yang
AU - Dongho Geum
AU - Hyun Kim
AU - Il-Joo Cho
AU - Sanghyuk Lee
AU - Jae Ryun Ryu
AU - Woong Sun
AB - 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.
BT - Advanced Science
DA - 2023
DO - 10.1002/advs.202301787
IS - 20
LA - en
N2 - 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.
PY - 2023
EP - 2301787
T2 - Advanced Science
TI - Symmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord-Like Organoid (pSCO) with Dorsoventral Organization
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202301787
VL - 10
Y2 - 2023-09-15
SN - 2198-3844
ER -