2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Emergence of Stem Cell‐Based Brain Organoids: Trends and Challenges

      1 , 2
      BioEssays
      Wiley

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recent developments in 3D cultures exploiting the self-organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex "assembloids," which are able to reveal cell diversities, microcircuits, and cell-cell interactions within their 3D organization. Here, the ways in which human brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed.

          Related collections

          Most cited references38

          • Record: found
          • Abstract: found
          • Article: not found

          Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture.

          Mouse embryonic stem (ES) cells are competent for production of all fetal and adult cell types. However, the utility of ES cells as a developmental model or as a source of defined cell populations for pharmaceutical screening or transplantation is compromised because their differentiation in vitro is poorly controlled. Specification of primary lineages is not understood and consequently differentiation protocols are empirical, yielding variable and heterogeneous outcomes. Here we report that neither multicellular aggregation nor coculture is necessary for ES cells to commit efficiently to a neural fate. In adherent monoculture, elimination of inductive signals for alternative fates is sufficient for ES cells to develop into neural precursors. This process is not a simple default pathway, however, but requires autocrine fibroblast growth factor (FGF). Using flow cytometry quantitation and recording of individual colonies, we establish that the bulk of ES cells undergo neural conversion. The neural precursors can be purified to homogeneity by fluorescence activated cell sorting (FACS) or drug selection. This system provides a platform for defining the molecular machinery of neural commitment and optimizing the efficiency of neuronal and glial cell production from pluripotent mammalian stem cells.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            In vitro differentiation of transplantable neural precursors from human embryonic stem cells.

            The remarkable developmental potential and replicative capacity of human embryonic stem (ES) cells promise an almost unlimited supply of specific cell types for transplantation therapies. Here we describe the in vitro differentiation, enrichment, and transplantation of neural precursor cells from human ES cells. Upon aggregation to embryoid bodies, differentiating ES cells formed large numbers of neural tube-like structures in the presence of fibroblast growth factor 2 (FGF-2). Neural precursors within these formations were isolated by selective enzymatic digestion and further purified on the basis of differential adhesion. Following withdrawal of FGF-2, they differentiated into neurons, astrocytes, and oligodendrocytes. After transplantation into the neonatal mouse brain, human ES cell-derived neural precursors were incorporated into a variety of brain regions, where they differentiated into both neurons and astrocytes. No teratoma formation was observed in the transplant recipients. These results depict human ES cells as a source of transplantable neural precursors for possible nervous system repair.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration

              Organoid techniques provide unique platforms to model brain development and neurological disorders. While several methods for recapitulating corticogenesis have been described, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, has been lacking until recently. Here, we describe the generation of MGE and cortex-specific organoids from human pluripotent stem cells that recapitulate the development of MGE and cortex domains respectively. Population and single-cell RNA-seq profiling combined with bulk ATAC-seq analyses revealed transcriptional and chromatin accessibility dynamics and lineage relationships during MGE and cortical organoid development. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, fusing region-specific organoids followed by live-imaging enabled analysis of human interneuron migration and integration. Together, our study provides a platform for generating domain-specific brain organoids, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development.
                Bookmark

                Author and article information

                Journal
                BioEssays
                BioEssays
                Wiley
                0265-9247
                1521-1878
                July 19 2019
                August 2019
                July 05 2019
                August 2019
                : 41
                : 8
                : 1900011
                Affiliations
                [1 ]Institut für Humangenetik, Universitätsklinikum DüsseldorfHeinrich‐Heine‐UniversitätUniversitätsstr. 1 40225 Düsseldorf Germany
                [2 ]IUF‐Leibniz Research Institute for Environmental Medicine40225 Düsseldorf Germany
                Article
                10.1002/bies.201900011
                31274205
                9008733f-ad7f-4107-a952-0ffd80b0c525
                © 2019

                http://creativecommons.org/licenses/by/4.0/

                http://doi.wiley.com/10.1002/tdm_license_1.1

                History

                Comments

                Comment on this article