DOI: 10.5061/dryad.6m905qgcm
title: Human myelinated brain organoids with integrated microglia as a model for myelin repair and remyelinating therapies

description: Oligodendrocytes, the myelinating cells of the central nervous system
 (CNS), are essential for the formation of myelin sheaths and pivotal for
 maintaining axonal integrity and conduction. Disruption of these cells and
 the myelin sheaths they produce is a hallmark of demyelinating conditions
 like Multiple Sclerosis or resulting from certain drug side effects,
 leading to profound neurological impairments. In this study, we created a
 human brain organoid comprising neurons, astrocytes, and myelinating
 oligodendrocytes. By integrating iPSC-derived microglia, we endowed the
 brain assembloid with immune characteristics. Our model enabled the
 investigation of demyelination and remyelination - a process in which
 myelin sheaths are regenerated - in a human context. Here, we provide a
 DIA proteomics dataset of two timepoints from human brain organoid samples
 comprising neurons, astrocytes, and myelinating oligodendrocytes. The
 dataset includes the cytosolic and nuclear fractions and biological
 replicates for each timepoint (N = 3 for week 4 and N = 4 for week 10).
description: # Human myelinated brain organoids with integrated microglia as a model
 for myelin repair and remyelinating therapies Dryad DOI:
 https://doi.org/10.5061/dryad.6m905qgcm Oligodendrocytes, the myelinating
 cells of the central nervous system (CNS), are essential for the formation
 of myelin sheaths and pivotal for maintaining axonal integrity and
 conduction. Disruption of these cells and the myelin sheaths they produce
 is a hallmark of demyelinating conditions like Multiple Sclerosis or
 resulting from certain drug side effects, leading to profound neurological
 impairments. In this study, we created a human brain organoid comprising
 neurons, astrocytes, and myelinating oligodendrocytes. By integrating
 iPSC-derived microglia, we endowed the brain assembloid with immune
 characteristics. Our model enabled the investigation of demyelination and
 remyelination - a process in which myelin sheaths are regenerated - in a
 human context. Our findings reveal that the integrated microglia were
 active participants in myelin repair, responding to demyelination with a
 robust inflammatory response, paving the way for regeneration. This was
 evidenced by the reduction of myelin following toxin-induced demyelination
 and subsequent self-driven remyelination. This data set is a DIA
 proteomics dataset of two timepoints from human brain organoid samples
 comprising neurons, astrocytes, and myelinating oligodendrocytes. The
 dataset includes the cytosolic and nuclear fractions and biological
 replicates for each timepoint (N = 3 for week 4 and N = 4 for week 10). ##
 Description of the data and file structure ### Spectronaut output The file
 "neuronal_organoids_spectronaut_protein_output.tsv" contains the
 protein-level spectronaut output. The most important columns are *
 "R.FileName": The sample identifier *
 "PG.ProteinGroups" The protein group identifier *
 "PG.Quantity": The protein abundance values * Additional columns
 provide information on quantification details and protein annotation as
 described in the [Spectronaut
 documentation](https://biognosys.com/resources/spectronaut-manual/) ###
 Filtered data used for analysis The files prefixed
 `neuronal_organoids_data_filtered` contain the data matrices, features,
 and sample annotations that were used for analysis. They have the
 following content *
 "neuronal_organoids_data_filtered_sample_annotation.tsv": the
 sample (column) annotation of the expression matrix. Row names of this
 file correspond to column names in the above data matrix. Columns in this
 file contain sample characteristics such as the sampling time. *
 SampleName: the sample identifier used in the protein abundance .gct files
 described below * group: the sample grouping (fraction and timepoint) *
 fraction: indicates whether the sample is from the nuclear or cytosolic
 fraction * week: a numeric for the collection time point in weeks *
 collection_time_point: the collection week as a character * Replicate: the
 replicate within the sample groups * specimen_description: HMBO *
 specimen_type: Organoids * readout_id: the raw file name for each sample *
 SampleDynamicRange: dynamic range across all proteins per sample *
 SampleMedian median: across all protein abundances per sample *
 PctProteinQuantifiable: Percentage of proteins quantified per sample *
 "neuronal_organoids_data_filtered_feature_annotation.tsv": the
 protein group (row) annotation of the expression matrix. Row names of this
 file correspond to row names in the above data matrix. Columns in this
 file contain protein information such as the number of unique peptides,
 peptide sequence, and protein annotation. * FeatureID: the row identifier
 used in the protein abundance .gct files described below. It also
 corresponds to "PG.ProteinGroups" in the Spectronaut output
 file. Protein groups can consist of more than one UniProt identifier,
 separated by ";". * Accession: first UniProt identifier of
 FeatureID * AdditionalAccessions: if exist, all other UniProt identifiers
 of FeatureID, otherwise NA * Description: gene description of the protein
 group * GeneName: corresponding gene name(s) of proteins in a protein
 group * ProteinName: the protein name(s) of proteins in a protein group *
 Organism: which organism a protein group was mapped to * UniquePeptides:
 number of unique peptides per protein group * Completeness: average
 quantification completeness of a protein group across all samples *
 Coverage: percent sequence coverage of a protein group * FeatureCV:
 coefficient of variation of a protein group * FeatureDynamicRange: dynamic
 range of a protein group * FeatureMedianAbundance: median abundance of a
 protein group across samples *
 "neuronal_organoids_data_filtered_imputed.gct": the protein
 abundance matrix in gct format. Rows correspond to protein groups, columns
 correspond to samples. Row identifiers are the FeatureIDs, column
 identifiers are the SampleNames. Missing values have been imputed using a
 mixed strategy (If only one sample is missing for a protein, the median
 value, 0.5 of the minimum, is imputed). *
 "neuronal_organoids_data_filtered_ibaq.gct": ibaq normalized
 version of the protein abundance matrix above in gct format. Row
 identifiers are the FeatureIDs, column identifiers are the SampleNames.
 For protein groups with more than one UniProt identifier, all values
 possible ibaq values (separated by ";") are given.