02581nas a2200469   4500000000100000000000100001008004100002260000900043653003000052653003300082653002600115653002500141653002200166100001500188700001400203700001700217700001400234700001600248700001800264700001400282700001800296700001600314700001600330700001700346700001700363700001600380700002000396700001700416700001600433700001600449700001300465700001500478700001700493700001700510700001400527245016400541856006700705300001200772490000700784520130600791022001402097       2023                            d  c202310adorsoventral organization10ahuman pluripotent stem cells10amicrocontact printing10aspinal cord organoid10asymmetry breaking1 aKyubin Seo1 aSubin Cho1 aHyogeun Shin1 aAeri Shin1 aJu-Hyun Lee1 aJune Hoan Kim1 aBoram Lee1 aHwanseok Jang1 aYoungju Kim1 aHyo Min Cho1 aYongdoo Park1 aHee Youn Kim1 aTaeseob Lee1 aWoong-Yang Park1 aYong Jun Kim1 aEsther Yang1 aDongho Geum1 aHyun Kim1 aIl-Joo Cho1 aSanghyuk Lee1 aJae Ryun Ryu1 aWoong Sun00aSymmetry Breaking of Human Pluripotent Stem Cells (hPSCs) in Micropattern Generates a Polarized Spinal Cord-Like Organoid (pSCO) with Dorsoventral Organization  uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202301787  a23017870 v103 aAxis 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.  a2198-3844