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Single-cell RNA sequencing of vascularized brain organoids

ABSTRACT: Single-cell RNA sequencing of vascularized brain organoids

PROVIDER: PRJNA427709 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6425161_1.fastq.gz	Fastqsanger.gz
	SRR6425161_2.fastq.gz	Fastqsanger.gz
	SRR6425162_1.fastq.gz	Fastqsanger.gz
	SRR6425162_2.fastq.gz	Fastqsanger.gz
	SRR6425163_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing of vascularized brain organoids

Project description:Organoids have been widely used as unique models of human brain development and disorders. However, the lack of vasculatures in brain orgnoids limits their application in the study of brain vasculature development and diseases. Here, we described to the generation of vascularized brain organoids (VBOrs) with different brain regions from human embryonic stem cells. The goals of this study are to analyze the cell populations of the new model of vasularized brain organoids cultured from human embryonic stem cells (H9). We found that VBOrs contain variant brain cells inculding neural progenitors, neuronal cells, astrocytes, sparse endothelial cells, and pericytes. The new model of VBOrs should be valuable for addressing questions between brain vasculatures and neural cells.

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Project description:Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of sEPSCs (spontaneous excitatory postsynaptic currents), sIPSCs (spontaneous inhibitory postsynaptic currents) and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, single-cell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.

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Project description:The human brain has changed dramatically from other primate species, but the genetic and developmental mechanisms behind the differences remains unclear. Here we used single cell RNA sequencing based on 10X technology to explore temporal transcriptomic dynamics and cellular heterogeneity in cerebral organoids derived from human and non-human primates chimpanzee and rhesus macaque stem cells. Using cerebral organoids as a proxy of early brain development, we detect a delayed pace of human brain development relative to the other two primate species. Additional human-specific gene expression patterns resolved to different cell states through progenitors to neurons are also found. Our data provide a transcriptomic cell atlas of primate early brain development, and illustrate features that are unique to humans.

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