Human-specific transposable elements shaped the evolution of craniofacial development through regulation of neural crest migration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1238839 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32788738_1.fastq.gz | Fastqsanger.gz | |||
| SRR32788738_2.fastq.gz | Fastqsanger.gz | |||
| SRR32788739_1.fastq.gz | Fastqsanger.gz | |||
| SRR32788739_2.fastq.gz | Fastqsanger.gz | |||
| SRR32788740_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Craniofacial development is evolutionarily conserved, yet subtle changes in its regulatory network drive species-specific traits. Transposable elements (TEs) contribute to genome evolution, but their role in cranial neural crest cells (CNCCs) remains unclear. Here, we investigate the domestication of hominoid-specific TEs (LTR5Hs and SVAs) as enhancers during human CNCC specification, a process critical for vertebrate craniofacial development. Using human iPSC-derived CNCCs, we identified ~515 hominoid-specific TEs functioning as enhancers, including ~250 human-specific, predominantly LTR5Hs. These elements are enriched for CNCC coordinator motifs, are bound by the CNCC signature factor TWIST1, and their enhancer activity appears largely CNCC-specific. CRISPR-interference targeting ~75% of these active TEs led to widespread transcriptional dysregulation of genes involved in neural crest migration, and two orthogonal functional assays confirmed that CNCC migration is impaired upon TE repression. Finally, genes near human-specific TEs showed higher expression in human CNCCs compared to chimpanzee CNCCs, but TE repression restored gene expression to chimpanzee levels. These findings highlight how young TEs were domesticated to fine-tune CNCC regulatory networks, potentially contributing to lineage-specific craniofacial evolution.
2025-03-23 | GSE292478 | GEO
Project description: Not available
| S-EPMC12673149 | biostudies-literature
Project description: Not available
| S-SCDT-10_1038-S44320-025-00151-Z | biostudies-other
Project description:The histone methyltransferase Polycomb repressive complex 2 (PRC2) is required for specification of the neural crest, and mis-regulation of neural crest development can cause severe congenital malformations. PRC2 is necessary for neural crest induction, but the embryonic, cellular, and molecular consequences of PRC2 activity after neural crest induction are incompletely understood. Here we show that Eed, a core subunit of PRC2, is required for craniofacial osteoblast differentiation and mesenchymal proliferation after induction of the neural crest. Integrating mouse genetics with single-cell RNA sequencing and epigenomic profiling, our results reveal that conditional knockout of Eed after neural crest cell induction causes severe craniofacial hypoplasia, impaired craniofacial osteogenesis, and attenuated craniofacial mesenchymal cell proliferation that is first evident in post-migratory neural crest cell populations. We show that Eed drives mesenchymal differentiation and proliferation in vivo and in primary craniofacial cell cultures by regulating diverse transcription factor programs that are required for specification of post-migratory neural crest cells. These data enhance understanding of epigenetic mechanisms that underlie craniofacial development, and shed light on the embryonic, cellular, and molecular drivers of rare congenital syndromes in humans.
2025-07-16 | GSE302601 | GEO
Project description:Knowledge of cell signaling pathways that drive human neural crest differentiation into craniofacial chondrocytes is incomplete, yet essential for using stem cells to regenerate craniomaxillofacial structures. To accelerate translational progress, we developed a differentiation protocol that generated self-organizing craniofacial cartilage organoids from human embryonic stem cell-derived neural crest stem cells. Histological staining of cartilage organoids revealed tissue architecture and staining typical of elastic cartilage. Protein and post-translational modification (PTM) mass spectrometry and snRNASeq data showed that chondrocyte organoids expressed robust levels of cartilage extracellular matrix (ECM) components: many collagens, aggrecan, perlecan, proteoglycans, and elastic fibers. We identified two populations of chondroprogenitor cells, mesenchyme cells and nascent chondrocytes and the growth factors involved in paracrine signaling between them. We show that ECM components secreted by chondrocytes not only create a structurally resilient matrix that defines cartilage, but also play a pivotal autocrine cell signaling role to determine chondrocyte fate.
2024-04-04 | PXD050668 | Pride
Project description:Craniofacial development involves regulation of a compendium of transcription factors, signaling molecules and epigenetic regulators. Histone deacetylases (HDACs) are involved in the regulation of cell proliferation, differentiation and homeostasis across a wide range of tissues, such as brain, cardiovascular system, muscular system, and skeletal system. However, functional role of Hdac4 during craniofacial development is still unclear. In this study, we investigated the effects of Hdac4 knockout in craniofacial skeletal development by conditionally disrupting the Hdac4 gene in cranial neural crest cells (CNCCs) using Cre-mediated recombination. Mice deficient in Hdac4 in CNCCs-derived osteoblasts demonstrated a dramatic decrease in bone formation in frontal bone. In vitro pre-osteoblasts (MC3T3-E1 cells) lacking Hdac4 exhibited reduced proliferation activity in association with dysregulation of cell cycle-related genes. These findings suggest that Hdac4 acts partially as a regulator of craniofacial skeletal development by positively regulating proliferation of CNCCs-derived osteoblasts.
2022-03-09 | GSE186707 | GEO
Project description:Heterozygous loss-of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, peripheral nerves and several organ systems like eyes, ears, nose and heart. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition is unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7Whi/+ and Chd7Whi/Whi) mouse embryos at day 9.5, the time point of neural crest cell migration. We identified 98 genes showing greater than two fold differences in expression (log2 fold-change) and a P-value to false discovery rate (FDR) < 0.05 between wild-type and Chd7Whi/Whi embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance like semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 and one of its target genes, namely semaphorin3a in Xenopus laevis embryos, we could show abnormalities in the migration of neural crest cells in vivo. Additionally, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7 negative CHARGE patients suggesting a role for SEMA3A in the pathogenesis of CHARGE syndrome. To identify genes that are affected by the absence of functional Chd7 at the time point of neural crest cell migration, the expression profiles of E9.5 wild-type, Chd7Whi/+ and Chd7Whi/Whi female mouse embryos were compared by whole-genome microarray analysis. Mouse embryos of the same sex were used to avoid sex-dependent gene expression effects. We performed microarray analysis by using the Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Agilent) on four biological replicates from each group.
2014-07-01 | E-GEOD-46591 | biostudies-arrayexpress
Project description:Alternative splicing (AS) creates proteomic diversity from a limited size genome by generating numerous transcripts from a single protein-coding gene. Tissue-specific regulators of AS are essential components of the gene regulatory network, required for normal cellular function, tissue patterning, and embryonic development. However, their cell-autonomous function in neural crest development has not been explored. Here, we demonstrate that splicing factor Rbfox2 is expressed in the neural crest cells (NCCs) and deletion of Rbfox2 in NCCs leads to cleft palate and defects in craniofacial bone development. RNA-Seq analysis revealed that Rbfox2 regulates splicing and expression of numerous genes essential for neural crest/craniofacial development. We demonstrate that Rbfox2-TGF-β-Tak1 signaling axis is deregulated by Rbfox2 deletion. Furthermore, restoration of TGF-β signaling by Tak1 overexpression can rescue the proliferation defect seen in Rbfox2 mutants. We also identified a positive feedback loop in which TGF-β signaling promotes expression of Rbfox2 in NCCs.
2019-07-26 | GSE127245 | GEO
Project description:Heterozygous loss-of function mutations in CHD7 (chromodomain helicase DNA-binding protein 7) lead to CHARGE syndrome, a complex developmental disorder affecting craniofacial structures, peripheral nerves and several organ systems like eyes, ears, nose and heart. Recently, it was demonstrated that CHD7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures. So far only few CHD7 target genes involved in neural crest cell development have been identified and the role of CHD7 in neural crest cell guidance and the regulation of mesenchymal-epithelial transition is unknown. Therefore, we undertook a genome-wide microarray expression analysis on wild-type and CHD7 deficient (Chd7Whi/+ and Chd7Whi/Whi) mouse embryos at day 9.5, the time point of neural crest cell migration. We identified 98 genes showing greater than two fold differences in expression (log2 fold-change) and a P-value to false discovery rate (FDR) < 0.05 between wild-type and Chd7Whi/Whi embryos. Interestingly, many misregulated genes are involved in neural crest cell and axon guidance like semaphorins and ephrin receptors. By performing knockdown experiments for Chd7 and one of its target genes, namely semaphorin3a in Xenopus laevis embryos, we could show abnormalities in the migration of neural crest cells in vivo. Additionally, we detected non-synonymous SEMA3A variations in 3 out of 45 CHD7 negative CHARGE patients suggesting a role for SEMA3A in the pathogenesis of CHARGE syndrome.
2014-07-01 | GSE46591 | GEO
Project description:Nuclear receptors are iteratively deployed during neural crest development, from pre-induction through differentiation stages. NR2F1 and NR2F2 in particular have been proposed as broad regulators of early neural crest gene expression in mammals, but the timing, extent, and redundancy of their developmental requirement has remained unclear, as Nr2f1 and Nr2f2 single mouse mutants present only minimal craniofacial phenotypes. Here we report the dynamic expression patterns of Nr2f1 and Nr2f2 in the mouse cranial neural crest from specification through post-migratory stages. Combined conditional knockout of both Nr2f1 and Nr2f2 in the neural crest with Wnt1-Cre or Pax3Cre caused severe midfacial clefting, loss of the maxilla and palate, and hypoplasticity of all other facial skeletal elements except the distal mandible. These perinatal phenotypes were rooted in a major shortage of pharyngeal arch mesenchyme at mid-gestation. This in turn traced to a deficiency of migrating neural crest cells, first evident in the trailing part of the first arch migratory stream at embryonic day 8.75. RNAseq at a slightly earlier stage revealed downregulation of many migratory neural crest genes, including a possible direct target, the phospholipase Plcg2. These findings reveal a vital requirement for NR2F1/2 within the later-forming cranial neural crest.
2025-10-15 | GSE295092 | GEO