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Cerebral organoids proteomics - Human Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities

ABSTRACT: Pluripotent stem cells (PSC) can differentiate inot any cell type of an organism. Their remarkable capability of self-organization enables the formation of three-dimensional structures that resembles miniature organs, including cerebral organoids. These organoids can recreate early steps of the human cerebral cortex development, and show great potential for modeling human diseases, particularly for those with a developmental component. This data evidences stem cell-derived cerebral organoids as a key model to study brain development and neurodevelopmental, neurodegenerative and neuropsychiatric diseases.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Multipotent Stem Cell, Cell Culture, Embryonic Stem Cell

SUBMITTER: Juliana Minardi Nascimento

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD011605 | Pride | 2019-11-15

REPOSITORIES: Pride

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Human Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities.

Nascimento Juliana Minardi JM Saia-Cereda Verônica M VM Sartore Rafaela C RC da Costa Rodrigo Madeiro RM Schitine Clarissa S CS Freitas Hercules Rezende HR Murgu Michael M de Melo Reis Ricardo A RA Rehen Stevens K SK Martins-de-Souza Daniel D

Frontiers in cell and developmental biology 20191128

The limited access to functional human brain tissue has led to the development of stem cell-based alternative models. The differentiation of human pluripotent stem cells into cerebral organoids with self-organized architecture has created novel opportunities to study the early stages of the human cerebral formation. Here we applied state-of-the-art label-free shotgun proteomics to compare the proteome of stem cell-derived cerebral organoids to the human fetal brain. We identified 3,073 proteins ...[more]

PMID: 31850342

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Project description:Cerebral organoids â three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells â have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).

Dataset Information

Cerebral organoids proteomics - Human Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities

Publications

Human Cerebral Organoids and Fetal Brain Tissue Share Proteomic Similarities.

Similar Datasets

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