Expression profiles of the four human major ectodermal lineages
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101661 | GEO | 2017/09/08
SECONDARY ACCESSION(S): PRJNA395097
REPOSITORIES: GEO
Similar Datasets
Project description:During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure. To identify what type of signaling pathways and transcriptional factors are involved in the fate specification between SE and NE cells during neurulation.
2015-04-17 | E-GEOD-67977 | biostudies-arrayexpress
Project description:During primary neurulation, the separation of a single-layered ectodermal sheet into the surface ectoderm (SE) and neural tube specifies SE and neural ectoderm (NE) cell fates. The mechanisms underlying fate specification in conjunction with neural tube closure are poorly understood. Here, by comparing expression profiles between SE and NE lineages, we observed that uncommitted progenitor cells, expressing stem cell markers, are present in the neural plate border/neural fold prior to neural tube closure.
2015-04-17 | GSE67977 | GEO
Project description:The goal of the current NS23158 funding is to understand how neural fate-stabilizing (NFS) genes function in order to provide fundamental knowledge about their potential roles in neural stem cell development. Neural fate-stabilization is characterized by the expansion of the neural ectoderm shortly after it has been induced by the repression BMP signaling. During this time period a number of early-expressed NFS genes are expressed, each of which expands the neural plate in gain-of-function assays. But, we do not know how these genes are related to one another or whether they are arranged in a linear gene pathway or multi-path hierarchy. One aim of this grant is to elucidate the relationship of Six1, an early-expressed NFS gene that we cloned, to other NFS-genes. We propose to greatly enhance this analysis by utilizing DNA microarray analyses to identify unsuspected and novel target genes. What is the function of Six1 in establishing the lateral neural ectoderm, that gives rise to the placodes and how does it specifically relate to other NFS-genes? In the parent grant we proposed to study the relationship of NFS genes to one that we cloned, Six1 (Brugmann et al., 2004). Six1 expands the placodal ectoderm and holds it in an immature state. In the original grant, we proposed to study whether Six1 activates or suppresses the expression of 6 known lateral NFS genes, using PCR and in situ hybridization of animal caps and whole embryos. Herein we propose to use DNA microarray technology to reveal a much broader spectrum of potential target genes. Six1, a sine oculis transcription factor which is expressed in the early placodal ectoderm that gives rise to the cranial PNS, is a key regulator of neural placodal fate (Brugmann et al., 2004, Development). Being a newly cloned gene, we hypothesize that we will identify numerous downstream targets of Six1 by the proposed microarray analyses. This information will allow us to study their function by gain- and loss-of function studies in the whole embryo. Animal cap (AC) explants are a naïve embryonic ectoderm that is removed from embryonic signaling centers. They allow one to perform gene induction assays in the absence of confounding growth factors, and thus are ideal for identifying downstream targets of transcription factors. In this experiment we will take a gain-of-function approach to identify which genes are induced/repressed by Six1. Six1 mRNA (400pg) will be injected at the 2-cell stage, and embryos cultured until stage 8, at which time the zygotic genome begins transcription. AC explants will be cut from the embryos and cultured in Normal Amphibian�s Medium. When ACs reach stage 10.5, an early step in neural ectoderm specification, they will be cultured in 200ng/nl Noggin protein (R&D Systems) to induce the expression of neural plate genes. When ACs reach stage 16, at which time the placodes have formed, they will be snap frozen in liquid nitrogen and RNA purified according to the Qiagen Rneasy Protect kit protocols. Our preliminary experiments indicate that 8-10ug of total RNA can be recovered with high purity from ~150 ACs with this method. As controls, RNA will be purified from uninjected animal caps, also treated with Noggin, derived from sibling embryos. We will repeat the experiment 5 times (total of 10 samples). Extracted RNA will be evaluated for quality, reverse transcribed into cDNA, amplified, fragmented and then biotinylated using the NuGEN Ovation Biotin System kit.
2008-06-11 | E-GEOD-11144 | biostudies-arrayexpress
Project description:Treatment-induced neuroendocrine transdifferentiation (NEtD) complicates therapies for metastatic prostate cancer (PCa). We propose that NEtD requires first an intermediary reprogramming to metastable cancer stem-like cells (CSCs) and showed that AR+/PSA+ PCa cell lines were efficiently reprogrammed to and maintained as CSCs by growth in androgen-free neural/neural crest (N/NC) stem medium. Such reprogrammed CSCs overexpressed stem genes, had features of N/NC stem cells, high tumor-initiating potential, resistance to anti-androgen and an EMT phenotype. Serum-containing mediums allowed re-differentiation to N-/NC-derived cell lineages or return back to PCa-like cancer cells. Once returned, the cells had increased resistance to androgen signaling inhibition. Finally, a 62-gene signature derived from reprogrammed PCa cell lines distinguished tumors from PCa patients with adverse outcomes. Gene expression profiles were obtained for RNAs extracted from biological replicates of parental LNCaP cells or from Neuroendocrine-like LNCaP (LNCaP-NE) cells grown for 15 days in CSS-media with no androgen.
2016-03-11 | E-GEOD-66851 | biostudies-arrayexpress
Project description:Neural crest (NC) is a vertebrate-specific embryonic progenitor cell population at the basis of important vertebrate features such as the craniofacial skeleton and pigmentation patterns. Despite the wide-ranging variation of NC-derived traits across vertebrates, the contribution of NC to species diversification remains underexplored. Here, leveraging the adaptive diversity of African Great Lakes' cichlid species, we combined comparative transcriptomics and population genomics to investigate the evolution of the NC genetic program in the context of their morphological divergence. Our analysis revealed substantial differences in transcriptional landscapes across somitogenesis, an embryonic period coinciding with NC development and migration. This included dozens of genes with described functions in the vertebrate NC gene regulatory network, several of which showed signatures of positive selection. Among candidates showing between-species expression divergence, we focused on teleost-specific paralogs of the NC-specifier sox10 (sox10a and sox10b) as prime candidates to influence NC development. These genes, expressed in NC cells, displayed remarkable spatio-temporal variation in cichlids, suggesting their contribution to interspecific morphological differences, such as craniofacial structures and pigmentation. Finally, through CRISPR/Cas9 mutagenesis, we demonstrated the functional divergence between cichlid sox10 paralogs, with the acquisition of a novel skeletogenic function by sox10a. When compared with teleost models zebrafish and medaka, our findings reveal that sox10 duplication, although retained in most teleost lineages, had variable functional fates across their phylogeny. Altogether, our study suggests that NC-related processes—particularly those controlled by sox10s—are involved in generating morphological diversification between species and lays the groundwork for further investigations into the mechanisms underpinning vertebrate NC diversification.
2024-08-18 | GSE250387 | GEO
Project description:SOX10 plays important roles in development of neural crest lineages and melanocyte lineages. SOX10 binding sites on chromatin have been characterized in glial lineages, but fewer focused on melanoma. To examine chromatin occupancy of SOX10 and chromatin landscape in melanoma, we performed ChIP-seq analysis of SOX10 and H3K27ac in SOX10-dependent melanoma SKMEL5. We confirmed SOX10 binding in genes previously reported as direct targets of SOX10, including ERBB3 and IL16. Importantly, SOX10 chemical probe (SH-0029) treatment abrogated the expression of these genes, suggesting that pharmacological perturbation of SOX10 modifies SOX10 transcriptional network and downregulates SOX10 target genes.
2024-04-24 | GSE256464 | GEO
Project description:The goal of the current NS23158 funding is to understand how neural fate-stabilizing (NFS) genes function in order to provide fundamental knowledge about their potential roles in neural stem cell development. Neural fate-stabilization is characterized by the expansion of the neural ectoderm shortly after it has been induced by the repression BMP signaling. During this time period a number of early-expressed NFS genes are expressed, each of which expands the neural plate in gain-of-function assays. But, we do not know how these genes are related to one another or whether they are arranged in a linear gene pathway or multi-path hierarchy. One aim of this grant is to elucidate the relationship of Six1, an early-expressed NFS gene that we cloned, to other NFS-genes. We propose to greatly enhance this analysis by utilizing DNA microarray analyses to identify unsuspected and novel target genes. What is the function of Six1 in establishing the lateral neural ectoderm, that gives rise to the placodes and how does it specifically relate to other NFS-genes? In the parent grant we proposed to study the relationship of NFS genes to one that we cloned, Six1 (Brugmann et al., 2004). Six1 expands the placodal ectoderm and holds it in an immature state. In the original grant, we proposed to study whether Six1 activates or suppresses the expression of 6 known lateral NFS genes, using PCR and in situ hybridization of animal caps and whole embryos. Herein we propose to use DNA microarray technology to reveal a much broader spectrum of potential target genes. Six1, a sine oculis transcription factor which is expressed in the early placodal ectoderm that gives rise to the cranial PNS, is a key regulator of neural placodal fate (Brugmann et al., 2004, Development). Being a newly cloned gene, we hypothesize that we will identify numerous downstream targets of Six1 by the proposed microarray analyses. This information will allow us to study their function by gain- and loss-of function studies in the whole embryo. Animal cap (AC) explants are a naïve embryonic ectoderm that is removed from embryonic signaling centers. They allow one to perform gene induction assays in the absence of confounding growth factors, and thus are ideal for identifying downstream targets of transcription factors. In this experiment we will take a gain-of-function approach to identify which genes are induced/repressed by Six1. Six1 mRNA (400pg) will be injected at the 2-cell stage, and embryos cultured until stage 8, at which time the zygotic genome begins transcription. AC explants will be cut from the embryos and cultured in Normal Amphibians Medium. When ACs reach stage 10.5, an early step in neural ectoderm specification, they will be cultured in 200ng/nl Noggin protein (R&D Systems) to induce the expression of neural plate genes. When ACs reach stage 16, at which time the placodes have formed, they will be snap frozen in liquid nitrogen and RNA purified according to the Qiagen Rneasy Protect kit protocols. Our preliminary experiments indicate that 8-10ug of total RNA can be recovered with high purity from ~150 ACs with this method. As controls, RNA will be purified from uninjected animal caps, also treated with Noggin, derived from sibling embryos. We will repeat the experiment 5 times (total of 10 samples). Extracted RNA will be evaluated for quality, reverse transcribed into cDNA, amplified, fragmented and then biotinylated using the NuGEN Ovation Biotin System kit. Keywords: neural fate, noggin, Six-1
2008-04-12 | GSE11144 | GEO
Project description:The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harbouring neural crest and cranial placode progenitors. Here we profile avian epiblast cells as a function of time using single-cell RNA-seq to define transcriptional changes in the emerging ‘neural plate border’. The results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridization. Developmental trajectory analysis shows that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker Pax7 contribute to multiple lineages, and a subset of premigratory neural crest cells shares a transcriptional signature with their border precursors. Together, our results suggest that cells at the neural plate border remain heterogeneous until early neurulation, at which time progenitors become progressively allocated toward defined lineages.
2021-12-31 | GSE181577 | GEO
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.
2022-07-01 | GSE199440 | GEO
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.
2022-07-01 | GSE199439 | GEO