The promise of organoids for unraveling the proteomic landscape of the developing human brain

The Brain Protein Atlas: A conglomerate of proteomics datasets of human neural tissue

“…Conversely, some analytical obstacles have been recently overcome by genomic approaches but will likely continue to remain hurdles for protein‐based technologies for the foreseeable future. Perhaps one of the significant challenges to characterizing brain tissue, in general, is its inaccessibility during in utero life, a highly dynamic period of brain development where critical milestones are largely completed, including neurogenesis and the subsequent formation of synapses (synaptogenesis) [20]. Similarly, even in pathological states, such as neurodegeneration and malignancies, the brain's critical function and thick boney covering translates to biopsies and resections often occurring only once in disease progression and very late in disease evolution (sometimes only at necropsy).…”

“…Another solution to these temporal challenges has more recently been offered by developing highly sophisticated in vitro experimental systems in which bioengineered brain tissue, in the form of cerebral organoids, can be generated and used to faithfully model many vital aspects of early brain development [30][31][32][33][34]. Unlike traditional adherent and simple suspension cultures of neural cells, these threedimensional structures of developing neural tissue, often benefiting from extra-cellular collagenous scaffolds like Matrigel, form complex cytoarchitectures that mirror subventricular-like neural progenitor regions, layered maturing cortical tissue, and even additional brain structures like choroid plexus and retinal elements [20,35]. Importantly, these humanoid tissue structures appear to mirror the biology of many human neuropathological states that cannot be captured in animal models, such as autism [36], zika virus [37], microcephaly [33],…”

Generation of cell-type-specific proteomes of neurodevelopment from human cerebral organoids

“…LC-MS/MS-based proteomics coupled with the brain organoid system provide new avenues of investigation in identifying neural lineage commitment and probe dynamic proteome changes across normal cellular differentiation states during human brain development and disease ( Melliou et al., 2021 ). Indeed, one of the SOX2-enriched proteins (RuvB like AAA ATPase 2) that we identified and investigated in our original study, didn’t appear to be enriched in this cell compartment at the mRNA level.…”