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@ARTICLE{Carido:265755,
      author       = {Carido, Madalena and Völkner, Manuela and Steinheuer, Lisa
                      Maria and Wagner, Felix and Kurth, Thomas and Dumler,
                      Natalie and Ulusoy, Selen and Wieneke, Stephanie and
                      Norniella, Anabel Villanueva and Golfieri, Cristina and
                      Khattak, Shahryar and Schoenfelder, Bruno and Scamozzi,
                      Maria and Zoschke, Katja and Canzler, Sebastian and
                      Hackermüller, Jörg and Ader, Marius and Karl, Mike O},
      title        = {{R}eliability of human retina organoid generation from
                      hi{PSC}-derived neuroepithelial cysts.},
      journal      = {Frontiers in cellular neuroscience},
      volume       = {17},
      issn         = {1662-5102},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {DZNE-2023-01030},
      pages        = {1166641},
      year         = {2023},
      abstract     = {The possible applications for human retinal organoids
                      (HROs) derived from human induced pluripotent stem cells
                      (hiPSC) rely on the robustness and transferability of the
                      methodology for their generation. Standardized strategies
                      and parameters to effectively assess, compare, and optimize
                      organoid protocols are starting to be established, but are
                      not yet complete. To advance this, we explored the
                      efficiency and reliability of a differentiation method,
                      called CYST protocol, that facilitates retina generation by
                      forming neuroepithelial cysts from hiPSC clusters. Here, we
                      tested seven different hiPSC lines which reproducibly
                      generated HROs. Histological and ultrastructural analyses
                      indicate that HRO differentiation and maturation are
                      regulated. The different hiPSC lines appeared to be a larger
                      source of variance than experimental rounds. Although
                      previous reports have shown that HROs in several other
                      protocols contain a rather low number of cones, HROs from
                      the CYST protocol are consistently richer in cones and with
                      a comparable ratio of cones, rods, and Müller glia. To
                      provide further insight into HRO cell composition, we
                      studied single cell RNA sequencing data and applied CaSTLe,
                      a transfer learning approach. Additionally, we devised a
                      potential strategy to systematically evaluate different
                      organoid protocols side-by-side through parallel
                      differentiation from the same hiPSC batches: In an
                      explorative study, the CYST protocol was compared to a
                      conceptually different protocol based on the formation of
                      cell aggregates from single hiPSCs. Comparing four hiPSC
                      lines showed that both protocols reproduced key
                      characteristics of retinal epithelial structure and cell
                      composition, but the CYST protocol provided a higher HRO
                      yield. So far, our data suggest that CYST-derived HROs
                      remained stable up to at least day 200, while single
                      hiPSC-derived HROs showed spontaneous pathologic changes by
                      day 200. Overall, our data provide insights into the
                      efficiency, reproducibility, and stability of the CYST
                      protocol for generating HROs, which will be useful for
                      further optimizing organoid systems, as well as for basic
                      and translational research applications.},
      keywords     = {gliosis (Other) / hiPSC (Other) / human (Other) /
                      neurodevelopment (Other) / organoid (Other) / pathology
                      (Other) / retina (Other) / stem cells (Other)},
      cin          = {AG Karl},
      ddc          = {610},
      cid          = {I:(DE-2719)1710004},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37868194},
      pmc          = {pmc:PMC10587494},
      doi          = {10.3389/fncel.2023.1166641},
      url          = {https://pub.dzne.de/record/265755},
}