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Uncovering the role of FOXA2 in the development of human serotonin neurons [scRNA-seq]

ABSTRACT: Uncovering the role of FOXA2 in the development of human serotonin neurons [scRNA-seq]

PROVIDER: PRJNA973600 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24633662_1.fastq.gz	Fastqsanger.gz
	SRR24633662_2.fastq.gz	Fastqsanger.gz
	SRR24633663_1.fastq.gz	Fastqsanger.gz
	SRR24633663_2.fastq.gz	Fastqsanger.gz

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Uncovering the role of FOXA2 in the development of human serotonin neurons [scRNA-seq]

Project description:We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of serotonin neurons derived from human pluripotent stem cells (hPSCs) and to compare the transcriptomic differences between FOXA2 knockout and wide type hPSCs-derived serotonin neurons.

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Uncovering the role of FOXA2 in the development of human serotonin neurons [RNA-seq]

Project description:Serotonin neurons (SNs) play a pivotal role in regulating brain development and function. Directed differentiation of SNs from human pluripotent stem cells (hPSCs) provides a useful tool for uncovering the mechanism of human SN development and the associated neuropsychiatric disorders. Previous studies reported that Foxa2 was expressed by serotonergic progenitors and functioned as a serotonergic fate determinant in mouse. However, the role of FOXA2 in human SNs development is unknown. Herein, we uncovered the role of FOXA2 through direct differentiation of FOXA2 lineage-tracing, FOXA2-knockout or inducible FOXA2-overexpression hPSCs into SNs. We found that SNs were not derived from FOXA2-lineage cells and FOXA2-knockout cells could still differentiate into mature and functional SNs, whereas FOXA2-overexpression enhanced the differentiation of floor plate (FP) cells rather than SNs. Coactivation of Sonic Hedgehog (SHH) and Retinoic acid (RA) signaling pathways promoted the differentiation towards SNs. In conclusion, FOXA2 is not intrinsically required for human SNs differentiation and simultaneous activation of SHH and RA signaling pathways could improve human SN differentiation by suppressing the differentiation towards FOXA2-positive FP cells. This study innovatively uncovers the role of FOXA2 in human SN development and provides a more efficient strategy to generate human SNs.

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Uncovering the role of FOXA2 in the development of human serotonin neurons

Project description:Uncovering the role of FOXA2 in the development of human serotonin neurons

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Uncovering the role of FOXA2 in the development of human serotonin neurons [RNA-seq]

Project description:Uncovering the role of FOXA2 in the development of human serotonin neurons [RNA-seq]

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Single-Cell Transcriptomes and Whole-Brain Projections of Serotonin Neurons in the Mouse Dorsal and Median Raphe Nuclei

Project description:We performed a comprehensive survey of DR and MR serotonin neurons in the adult mouse brain by scRNA-seq. To specifically label serotonin neurons, we crossed Sert-Cre mice (Gong et al., 2007) with the tdTomato Cre reporter mouse, Ai14 (Madisen et al., 2010). (Serotonin transporter, or Sert, is a marker for serotonin neurons; see more details below.) We collected serotonin neurons acutely dissociated from brain slices by fluorescence-activated cell sorting (FACS) and used Smart-seq2 (Picelli et al., 2013) to generate scRNA-seq libraries.

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Project description:Directed differentiation of serotonin neurons (SNs) from human pluripotent stem cells (hPSCs) provides a valuable tool for uncovering the mechanism of human SN development and the associated neuropsychiatric disorders. Previous studies report that FOXA2 is expressed by serotonergic progenitors (SNPs) and functioned as a serotonergic fate determinant in mouse. However, in the routine differentiation experiments, it is accidentally found that less SNs and more non-neuronal cells are obtained from SNP stage with higher percentage of FOXA2-positive cells. This phenomenon prompted them to question the role of FOXA2 as an intrinsic fate determinant for human SN differentiation. Herein, by direct differentiation of engineered hPSCs into SNs, it is found that the SNs are not derived from FOXA2-lineage cells; FOXA2-knockout hPSCs can still differentiate into mature and functional SNs with typical serotonergic identity; FOXA2 overexpression suppresses the SN differentiation, indicating that FOXA2 is not intrinsically required for human SN differentiation. Furthermore, repressing FOXA2 expression by retinoic acid (RA) and dynamically modulating Sonic Hedgehog (SHH) signaling pathway promotes human SN differentiation. This study uncovers the role of FOXA2 in human SN development and improves the differentiation efficiency of hPSCs into SNs by repressing FOXA2 expression.

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Project description:Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling [scRNA-seq]

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