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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE232698 | GEO | 2023/09/07

REPOSITORIES: GEO

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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.

2023-09-07 | GSE214605 | GEO

Expression Profile of Embryonic Stem Cell Derived Serotonin Neurons

Project description:The rhesus embryonic stem cell line 366.4 differentiates into serotonin neurons. RNA was extracted from ESC colonies, embryoid body (Ebs), Neurospheres in selection (N1), Proliferating serotonin neurons (N2) and differentiating serotonin neurons (N3). RNA was labeled with Enzo biotin labelling kit and hybridized to Rhesus chip from Affymetrix. single sample represent each stages and total 5 rhesus chip were hybridized

2010-04-08 | E-GEOD-16168 | biostudies-arrayexpress

Expression Profile of Embryonic Stem Cell Derived Serotonin Neurons

2009-05-21 | GSE16168 | GEO

Generation of caudal-type serotonin neurons and hindbrain fate organoids from hPSCs

Project description:Generation of caudal-type serotonin neurons and hindbrain fate organoids from hPSCs

| PRJNA704049 | ENA

Generation of caudal-type serotonin neurons and hindbrain fate organoids from hPSCs

Project description:Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on the anatomical location and axonal projection, 5-HT neurons are coarsely divided into rostral and caudal groups. Here, we propose a novel strategy to generate hindbrain 5-HT neurons from human pluripotent stem cells (hPSCs), which involves the formation of ventral-type neural progenitor cells (NPCs) and stimulation of the hindbrain 5-HT neural development. A caudalizing agent, retinoid acid (RA), was used to direct the cells into the hindbrain cell fate. Approximately 30-40% of hPSCs successfully developed into 5-HT-expressing neurons using our protocol, with the majority acquiring a caudal rhombomere identity (r5-8). We further modified our monolayer differentiation system to generate 5-HT neuron-enriched hindbrain-like organoids. We have also suggested downstream applications of our 5-HT monolayer and organoid cultures to study neuronal response to gut microbiota. Our methodology could become a powerful tool for future studies related to 5-HT neurotransmission.

2021-04-01 | GSE167278 | GEO

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.

2019-08-01 | GSE135132 | GEO

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-09-07 | GSE232830 | GEO

Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons

Project description:Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons

| PRJNA517131 | ENA

Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons

Project description:The goals of this study are to generate and study neurons from MDD patients and examine specific aspects of serotonergic neurotransmission in selective serotonin reuptake inhibitor (SSRI) remitters ® and SSRI-nonremitters (NR)

2019-12-04 | GSE125664 | GEO

Generation of a TPH2-EGFP reporter cell line for Purification and Monitoring of Human Serotonin neurons in vitro and in vivo

Project description:Generation of serotonin neurons (SNs) from human pluripotent stem cells (hPSCs) provides a promising platform to explore the mechanisms of serotonin-associated neuropsychiatric disorders. However, neural differentiation always yields heterogeneous cell populations, making it difficult to identify and purify SNs in vitro or track them in vivo following transplantation. Herein, we generated a TPH2-EGFP reporter hPSC line with insertion of EGFP into the endogenous tryptophan hydroxylase 2 (TPH2) locus using CRISPR-Cas9-mediated gene editing technology. This TPH2-reporter, which faithfully indicated TPH2 expression during differentiation, enabled us to obtain purified SNs for subsequent transcriptional analysis and study of pharmacological responses to antidepressants. In addition, the reporter system showed strong EGFP expression to indicate SNs, which enabled us to explore in vitro and ex vivo electrophysiological properties of SNs. In conclusion, this TPH2-EGFP reporter cell line might be of great significance for studies on human SN-related development and differentiation, drug screening, disease modeling, and cell replacement therapies.

2022-09-22 | GSE206341 | GEO

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