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Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

ABSTRACT: Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

PROVIDER: PRJNA1012310 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25887055_1.fastq.gz	Fastqsanger.gz
	SRR25887055_2.fastq.gz	Fastqsanger.gz
	SRR25887056_1.fastq.gz	Fastqsanger.gz
	SRR25887056_2.fastq.gz	Fastqsanger.gz
	SRR25887057_1.fastq.gz	Fastqsanger.gz

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Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

2023-10-23 | GSE242228 | GEO

Transcriptomic Profiling of Vagal and Sacral Level Neural Crest Cell from Mouse Embryos Using Next Generation Sequencing

Project description:The ENS of vertebrates develops from neural crest cell (NCC) deriving from mainly the vagal neural crest, while NCCs from the sacral level to a less extent. In mouse embryos, the vagal NCCs emigrate from the neural tube adjacent to the somite level from 1-7 at Embryonic day (E)9.0, and sacral NCCs emigrate from the neural tube adjacent to the level of somites caudal to somite 24 in the mouse (in the chick, caudal to somite 28) at E9.5. The spatial difference in cell colonization between vagal and sacral NCCs is that vagal NCCs completely colonize the whole gut, while the distribution of sacral NCCs is only restricted to the hindgut segment. To determine the differences between these two groups of cells, we isolated vagal and sacral NCCs by neural tube explant culture and then performed high-throughput RNA-seq to examine the transcriptional variation. We analyzed that differentially expressed genes (DEGs) by gene ontology (GO) analysis in which the DEGs were enriched in cell adherin, proliferation, transcriptional regulation, et al. This study might help to explore the underlying basis for the different cell behaviors between vagal and sacral NCCs during mouse embryonic development.

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hPSC-derived Sacral Neural Crest Enables Rescue in a Severe Model of Hirschsprung’s Disease [ATAC-seq]

Project description:The enteric nervous system (ENS) is derived from both the vagal and sacral component of the neural crest (NC). Here, we present the derivation of sacral ENS precursors from human PSCs via timed exposure to FGF, WNT and to GDF11 to enable posterior patterning and transition from posterior trunk to sacral NC identity respectively. Using a SOX2::H2B-tdTomato/ T::H2B-GFP dual reporter hPSC line, we demonstrate that both trunk and sacral NC emerge from a double-positive neuro-mesodermal progenitor (NMP). Vagal and sacral NC precursors yield distinct neuronal subtypes and migratory behaviors in vitro and in vivo. Remarkably, xenografting of both vagal and sacral NC lineages is required to rescue a mouse model of total aganglionosis, suggesting novel opportunities in the treatment of severe forms of Hirschsprung’s disease.

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hPSC-derived Sacral Neural Crest Enables Rescue in a Severe Model of Hirschsprung’s Disease [RNA-seq]

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Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system.

Project description:During development, much of the enteric nervous system (ENS) arises from the vagal neural crest that emerges from the caudal hindbrain and colonizes the entire gastrointestinal tract. However, a second ENS contribution comes from the sacral neural crest that arises in the caudal neural tube and populates the post-umbilical gut. By coupling single-cell transcriptomics with axial-level-specific lineage tracing in avian embryos, we compared the contributions of embryonic vagal and sacral neural crest cells to the chick ENS and the associated peripheral ganglia (Nerve of Remak and pelvic plexuses). At embryonic day (E) 10, the two neural crest populations form overlapping subsets of neuronal and glia cell types. Surprisingly, the post-umbilical vagal neural crest much more closely resembles the sacral neural crest than the pre-umbilical vagal neural crest. However, some differences in cluster types were noted between vagal and sacral derived cells. Notably, RNA trajectory analysis suggests that the vagal neural crest maintains a neuronal/glial progenitor pool, whereas this cluster is depleted in the E10 sacral neural crest which instead has numerous enteric glia. The present findings reveal sacral neural crest contributions to the hindgut and associated peripheral ganglia and highlight the potential influence of the local environment and/or developmental timing in differentiation of neural crest-derived cells in the developing ENS.

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Analysis of gene expression in Sox10 Dom mutant sacral neural crest cells

Project description:Hirschsprung’s disease (HSCR) is a congenital disease which is characterized by the reduction or absence of neurons and glial cells in the enteric nervous system (ENS). Failure of neural crest cells (NCCs) to colonize the gut during the embryonic development has been considered as one of the possible causes of the disease. In this study, the migration and gene expression of sacral NCCs from the spontaneous mouse mutant Dominant megacolon (Dom) which is a HSCR animal model expressing a mutated transcription factor Sox10, were analyzed in order to identify candidate genes which may possibly affect the NCC migration in the mutant.

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Transcriptomic Profiling of Vagal and Sacral Level Neural Crest Cell from Mouse Embryos Using Next Generation Sequencing

Project description:Transcriptomic Profiling of Vagal and Sacral Level Neural Crest Cell from Mouse Embryos Using Next Generation Sequencing

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Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages

Project description:The enteric nervous system (ENS) predominantly originates from vagal neural crest cells (VNC) that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally-specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies.

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Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages

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Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages [scRNA-seq]

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