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Defining the nature of human pluripotent stem cell-derived interneurons via single cell analysis

ABSTRACT: Defining the nature of human pluripotent stem cell-derived interneurons via single cell analysis

PROVIDER: PRJNA753092 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15376016_1.fastq.gz	Fastqsanger.gz
	SRR15376016_2.fastq.gz	Fastqsanger.gz
	SRR15376017_1.fastq.gz	Fastqsanger.gz
	SRR15376017_2.fastq.gz	Fastqsanger.gz
	SRR15376018_1.fastq.gz	Fastqsanger.gz

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Defining the nature of human pluripotent stem cell-derived interneurons via single cell analysis

Project description:Defining the nature of human pluripotent stem cell-derived interneurons via single cell analysis

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Defining the nature of human pluripotent stem cell-derived interneurons via single cell analysis

Project description:We applied single nuclei and single cell transcriptomics methods to model interneuron development with interneurons derived from human PSCs. We find that PSC-derived interneurons capture stages of development prior to mid gestation, but only represent a minority of potential subtypes that are found in the brain. Comparison of these interneurons to those found in the adult brain highlighted decreased expression of synapse-related genes, reflective of their electrophysiological immaturity. Together, these analyses provide a full characterization of PSC-derived interneurons.

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Project description:Defining how human pluripotent cell identity is controlled and in particular how naïve pluripotency is acquired during cell reprogramming is crucial for the future applications of pluripotent stem cells. However, the regulatory pathways of naïve cell reprogramming remain incompletely understood. Here, we used genome-wide CRISPR-Cas9 screening to identify novel regulators of primed to naïve pluripotent stem cell reprogramming, including genes that are essential for reprogramming and genes that normally impede reprogramming and whose targeted deletion led to enhanced reprogramming. Integrated analysis defined specific chromatin complexes and signalling pathways as critical regulators of naïve reprogramming, and were largely distinct from regulators of somatic cell reprogramming. Mechanistically, PRC1.3 and PRDM14 are jointly required to transcriptionally repress developmental and gene regulatory factors to ensure naïve cell reprogramming. Additionally, small molecule inhibitors of reprogramming impediments increased the efficiency of naïve cell reprogramming, and are of practical benefit that can improve on current reprogramming methods. Taken together, we have identified novel regulators controlling the establishment of naïve pluripotency in human cells, which will open up new ways to exploit the full potential of pluripotent stem cells. These results also provide new insights into mechanisms that destabilise and reconfigure cell identity during cell state transitions.

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