Foxa2 and Pet1 direct and indirect synergy drive serotonergic neuronal differentiation [ChIP-Seq]
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ABSTRACT:
PROVIDER: PRJNA819384 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18462579.fastq.gz | Fastqsanger.gz | |||
| SRR18462580.fastq.gz | Fastqsanger.gz | |||
| SRR18462581.fastq.gz | Fastqsanger.gz | |||
| SRR18462582.fastq.gz | Fastqsanger.gz | |||
| SRR18462583.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 14 |
Similar Datasets
Project description:Foxa2 and Pet1 direct and indirect synergy drive serotonergic neuronal differentiation
| PRJNA819381 | ENA
Project description:Neuronal programming by forced expression of transcription factors (TFs) holds promise for clinical applications of regenerative medicine. However, the mechanisms by which TFs coordinate their activities on the genome and control distinct neuronal fates remain obscure. Using direct neuronal programming of embryonic stem cells, we dissected the contribution of a series of TFs to specific neuronal regulatory programs. We deconstructed the Ascl1-Lmx1b-Foxa2-Pet1 TF combination that has been shown to generate serotonergic neurons and found that stepwise addition of TFs to Ascl1 canalizes the neuronal fate into a diffuse monoaminergic fate. The addition of pioneer factor Foxa2 represses Phox2b to induce serotonergic fate, similar to in vivo regulatory networks. Foxa2 and Pet1 appear to act synergistically to upregulate serotonergic fate. Foxa2 and Pet1 co-bind to a small fraction of genomic regions but mostly bind to different regulatory sites. In contrast to the combinatorial binding activities of other programming TFs, Pet1 does not strictly follow the Foxa2 pioneer. These findings highlight the challenges in formulating generalizable rules for describing the behavior of TF combinations that program distinct neuronal subtypes.
2022-06-09 | GSE199314 | GEO
Project description:Neuronal programming by forced expression of transcription factors (TFs) holds promise for clinical applications of regenerative medicine. However, the mechanisms by which TFs coordinate their activities on the genome and control distinct neuronal fates remain obscure. Using direct neuronal programming of embryonic stem cells, we dissected the contribution of a series of TFs to specific neuronal regulatory programs. We deconstructed the Ascl1-Lmx1b-Foxa2-Pet1 TF combination that has been shown to generate serotonergic neurons and found that stepwise addition of TFs to Ascl1 canalizes the neuronal fate into a diffuse monoaminergic fate. The addition of pioneer factor Foxa2 represses Phox2b to induce serotonergic fate, similar to in vivo regulatory networks. Foxa2 and Pet1 appear to act synergistically to upregulate serotonergic fate. Foxa2 and Pet1 co-bind to a small fraction of genomic regions but mostly bind to different regulatory sites. In contrast to the combinatorial binding activities of other programming TFs, Pet1 does not strictly follow the Foxa2 pioneer. These findings highlight the challenges in formulating generalizable rules for describing the behavior of TF combinations that program distinct neuronal subtypes.
2022-06-09 | GSE199313 | GEO
Project description:Foxa2 and Pet1 direct and indirect synergy drive serotonergic neuronal differentiation [ATAC-Seq]
| PRJNA819385 | ENA
Project description:Neuronal programming by forced expression of transcription factors (TFs) holds promise for clinical applications of regenerative medicine. However, the mechanisms by which TFs coordinate their activities on the genome and control distinct neuronal fates remain obscure. Using direct neuronal programming of embryonic stem cells, we dissected the contribution of a series of TFs to specific neuronal regulatory programs. We deconstructed the Ascl1-Lmx1b-Foxa2-Pet1 TF combination that has been shown to generate serotonergic neurons and found that stepwise addition of TFs to Ascl1 canalizes the neuronal fate into a diffuse monoaminergic fate. The addition of pioneer factor Foxa2 represses Phox2b to induce serotonergic fate, similar to in vivo regulatory networks. Foxa2 and Pet1 appear to act synergistically to upregulate serotonergic fate. Foxa2 and Pet1 co-bind to a small fraction of genomic regions but mostly bind to different regulatory sites. In contrast to the combinatorial binding activities of other programming TFs, Pet1 does not strictly follow the Foxa2 pioneer. These findings highlight the challenges in formulating generalizable rules for describing the behavior of TF combinations that program distinct neuronal subtypes.
| S-EPMC9254625 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-06-09 | GSE199315 | GEO
Project description:Neurons must function for decades of life but how these non-dividing cells are preserved is poorly understood. Using mouse serotonin (5-HT) neurons as a model, we discovered a novel adult-stage transcriptional program specialized to ensure the preservation of serotonergic connectivity. We uncover a switch in Lmx1b and Pet1 transcription factor function from controlling embryonic axonal growth to sustaining a transcriptomic signature of serotonergic connectivity comprising functionally diverse synaptic and axonal genes. Adult-stage deficiency of Lmx1b and Pet1 caused slowly progressive degeneration of 5-HT synapses and axons, increased susceptibility of 5-HT axons to neurotoxic injury, and abnormal stress responses. Axon degeneration occurred in a die back pattern and was accompanied by accumulation of alpha-synuclein and APP in spheroids and mitochondrial fragmentation without cell body loss. Our findings suggest neuronal connectivity is transcriptionally protected by maintenance of connectivity transcriptomes; progressive decay of such transcriptomes may contribute to age-related diseases of brain circuitry.
2022-03-24 | GSE189052 | GEO
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
Project description:Mental disorders are caused by genetic and environmental factors. We here show that deficiency of an isoform of dopamine D2 receptor (D2R), D2LR, causes psychosocial stress vulnerability in mouse. This occurs through dysfunction of type 1A serotonin (5-hydroxytryptamine, 5-HT) receptor (5-HT1AR) on serotonergic neurons in the mouse brain. Exposure to forced swim stress significantly increased anxiety- and depressive-like behaviors in D2LR knockout (D2LR-KO) male mice as compared with wild-type mice. Treatment with 8-OH-DPAT, a 5-HT1AR agonist, failed to alleviate the stress-induced behaviors in D2LR-KO mice. In forced swim-stressed D2LR-KO mice, 5-HT release in the medial prefrontal cortex was elevated and the expression of genes related to 5-HT levels was up-regulated by the transcription factor PET1 in the dorsal raphe nucleus. Notably, D2LR formed a heteromer with 5-HT1AR in serotonergic neurons, thereby suppressing 5-HT1AR–activated G-protein–activated inwardly rectifying potassium (GIRK) conductance in D2LR-KO serotonergic neurons. Finally, D2LR overexpression in serotonergic neurons in the dorsal raphe nucleus alleviated stress vulnerability observed in D2LR-KO mice. Taken together, we conclude that disruption of the negative feedback regulation by the D2LR/5-HT1A heteromer causes stress vulnerability.
2019-01-09 | GSE124806 | GEO
Project description:Assembly of transcriptomes encoding unique neuronal identities requires selective accessibility of transcription factors to cis-regulatory sequences in nucleosome-embedded postmitotic chromatin. Yet, the mechanisms controlling postmitotic neuronal chromatin accessibility are poorly understood. Here, we show that unique distal enhancers define the Pet1 neuron lineage that generates serotonin (5-HT) neurons. Heterogeneous single cell chromatin landscapes are established early in postmitotic Pet1 neurons and reveal the putative regulatory programs driving Pet1 neuron subtype identities. Distal enhancer accessibility is highly dynamic as Pet1 neurons mature, suggesting the existence of regulatory factors that reorganize postmitotic neuronal chromatin. We find that Pet1 and Lmx1b control chromatin accessibility to select Pet1-lineage specific enhancers for 5-HT neurotransmission. Additionally, these factors are required to maintain chromatin accessibility during early maturation suggesting that postmitotic neuronal open chromatin is unstable and requires continuous regulatory input. Together our findings reveal postmitotic transcription factors that reorganize accessible chromatin for neuron specialization.
2022-04-14 | GSE185737 | GEO