In vitro overexpression of Nhp2, Emg1 and Tsr3 genes in iPSC-derived neural crest cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE308372 | GEO | 2025/12/01
REPOSITORIES: GEO
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Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
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Project description:The cranial neural crest cells are pluripotent cells that provide head skeletogenic mesenchyme and are crucial for craniofacial patterning. Here, we analyzed the in vivo chromatin landscapes of mouse cranial neural crest subpopulations. Early postmigratory neural crest subpopulations contributing to distinct mouse craniofacial structures displayed similar chromatin accessibility patterns, yet differed transcriptionally. Accessible promoters and enhancers of differentially silenced genes carried H3K27me3/H3K4me2 bivalent chromatin marks embedded in large Ezh2-dependent Polycomb domains, indicating transcriptional poising. These postmigratory bivalent regions were already present in neural crest premigratory progenitors. At Polycomb domains, H3K27me3 antagonized H3K4me2 deposition, which was restricted to accessible sites. Thus, bivalent Polycomb domains provide a chromatin template for the regulation of cranial neural crest cell positional identity in vivo contributing novel insights into the epigenetic regulation of face morphogenesis.
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Project description:The epithelial-to-mesenchymal transition (EMT) and migration of cranial neural crest cells are critical processes that occur in the early embryo that permit proper craniofacial patterning. Disruptions in these processes not only impair development but also lead to various diseases, underscoring the need for their detailed understanding at the molecular level. The chick embryo has served historically as an excellent model for human embryonic development. While chick cranial neural crest cell EMT and migration have been characterized at the transcript level, studies at the protein level—to allow direct measurement of the active players—have not been undertaken to date. In this study, we applied mass spectrometry (MS)-based proteomics to establish a deep proteomics profile of the midbrain region during early embryonic development. We developed a proteomics method combining optimal lysis conditions and offline fractionation with nanoflow liquid chromatography coupled to high-resolution MS to analyze the tissue from this region, which identified >5,900 proteins involved in key pathways related to neural crest cell EMT and migration such as signaling, proteolysis/extracellular matrix (ECM), and transcriptional regulation. This study offers valuable insight into important developmental processes occurring in the midbrain region and demonstrates the utility of proteomics for characterization of various tissues during chick embryogenesis.
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Project description:Mutations of NBS1 gene result in Nijmegen breakage syndrome (NBS), and the gene encodes NBS1 that forms a complex with MRE11 and RAD50 and participates in DNA damage repair. However, the molecular mechanism by which the mutations of NBS1 cause clinical phenotypes of NBS, such as craniofacial dysmorphism, is still unclear. Here, we show that NBS1 localizes at the rDNA loci in the nucleoli and interacts with ribosome RNA (rRNA) transcription machinery including RNA polymerase I (Pol I) and TCOF1. Loss of NBS1 impairs Pol I-dependent transcription of pre-rRNA and induces nucleolar stress. In particular, lacking Nbs1 in mouse neural crest cells not only leads to the reduction of ribosome biogenesis but also craniofacial abnormalities during prenatal development. Moreover, the C-terminus of NBS1 is associated with pre-rRNA and a number of pre-rRNA processing factors, which may also facilitate pre-rRNA maturation. Taken together, our study reveals the functions of NBS1 in rRNA biogenesis.
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Project description:Defects in ribosome biogenesis can trigger a battery of cellular events to alter gene expression and cell growth. 18S rRNA methyltransferase EMG1 is an important assembly factor in ribosome biogenesis. Here, we report that downregulation of EMG1 non-enzymatically leads to decreased N6-methyladensine (m6A) levels in polyadenylated RNA. We revealed the identities of the messenger RNAs with decreased m6A intensities upon EMG1 deficiency using m6A-IP-seq. This group of mRNAs significantly overlap with the CLIP targets of IGF2BP3, which is an m6A reader protein stabilizing m6A-containing transcripts. Furthermore, both RNA-seq and qRT-PCR results suggest that the expression level of this group of mRNAs significantly decreased upon EMG1 deficiency, possibly through the regulation of IGF2BP3. Gene ontology analysis suggests that this group of mRNAs function in a list of cell signaling pathways important for cell growth. These findings collectively suggest that decreased ribosome assembly may influence gene expression via decreasing m6A levels in mRNAs.
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