by various mutations of the X-linked proteolipid protein 1 gene (PLP1). PLP1 is a critical protein for myelin formation. PMD is classified as a leukodystrophy, meaning that it is a disease affecting the white matter of the brain. Madhavan et al. tested how well their myelinoid system could recapitulate the established cellular pathology of PMD. Organoids were derived from three patients with varying disease severity where the subject with a deletion, a duplication, and a point mutation had mild, moderate and severe phenotypes respectively. Their results demonstrated that the myelinating oligocortical spheroids generated recapitulated the degrees of cellular pathology associated with the genetic variants, therefore can serve as models for understanding the relationships between PMD genotypes and phenotypes, which have not been fully characterized yet. Neurofascin (NFASC) nonsense mutation The NFASC gene encodes a cell adhesion molecule that is involved in neurite outgrowth, fasciculation. Additionally, NFASC is involved in the organization of axonal initiation segment and the nodes of Ranvier during development. Patients with nonsense mutations in NFASC have abnormalities in the paranodal axo-glial junction (PNJ). James et al., demonstrated that patient derived myelinoids had widespread formation of myelinoids of both patient and control, however, as expected, the PNJ in patient derived myelinoids had disrupted paranode formation. Genome Analysis ‘Omics’ has a broad application to organoids and since the development of organoid technology, transcriptome, epigenome, proteome, and metabolome analysis have been used. Additionally, targeted gene editing and host-microbiome interactions have been studied using organoids. Single-Cell Omics For obvious reasons, it is not possible to study gene expression patterns of the brain in human subjects, so the ability to recapitulate some of the complexity of the human brain in vitro allows for aspects of human development and disease to be investigated. Single-cell omics is a powerful tool that has been used to identify different subpopulations of oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes in mouse models which were previously undefined. The heterogeneity of oligodendrocytes was previously thought to be functionally homogeneous, however, distinct cell populations can be characterized through specific transcriptional signatures and gene ontology profiles. Single-cell RNA sequencing (scRNA seq) analysis of myelinoids generated by Madhavan et al., confirmed that there were distinct populations of oligodendrocytes throughout multiple stages of development in oligocortical spheroids which closely matched the single-cell transcriptome data obtained from human fetal cortex. Due to their close transcriptomic resemblance to human fetal brain data, the regulatory landscape