New GEO Series

GSE330205 Gene expression pattern of K. phaffii GS115, hmt deficient and H2O2 treated strains

Sun, 10 May 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Komagataella phaffii GS115

Here we performed RNA-seq to examine gene expression difference in regular culture and H2O2 treated cells. Two strains were used here: GS115 (wild-type) and GS115-delta PAS_chr1-4_0287/PAS_chr1-1_0102/PAS_chr2-2_0494 (hmt deficient strain).

GSE330204 H3K36me3 enrichemnt on the genome of Komagataella phaffii GS115

Sun, 10 May 2026 00:00:00 -0400

Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Komagataella phaffii GS115

The goal of the study was to examine the the histone modification mark H3K36me3 occupancy in the ORF regions of K. phaffii.

GSE330111 Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome

Sun, 10 May 2026 00:00:00 -0400

Contributors : Xu Heng ; Chien Jo-Fan ; Kozlenkov Alexey ; Vadukapuram Ramu ; Li Junhao ; Wei Yu ; Dwork Andrew J. ; Liu Chunyu ; Dracheva Stella ; Mukamek Eran A.
Series Type : Methylation profiling by high throughput sequencing
Organism : Homo sapiens

Healthy brain development requires a coordinated process of postnatal cellular maturation throughout the first two decades of life that transforms neuronal morphology, connectivity, physiology, and gene expression. The maturation and stable maintenance of neuron identity is driven, in part, by large-scale reconfiguration of the neuronal DNA methylome. Neurons have uniquely high levels of 5-hydroxy-methyl-cytosine (hmC) compared to other cell types, yet the relative contributions of 5hmC and 5-methyl-cytosine (mC) remain unknown because most experimental assays do not distinguish these marks. We measured mC and hmC using bisulfite- and oxidative-bisulfite sequencing in excitatory and inhibitory neurons, along with mRNA and histone modifications, from the prefrontal cortex of 103 human donors, ranging from 38 days to 77 years of age. Up to half of all CG dinucleotides convert from mC to hmC in a gradual process extending throughout the first decade of life, dramatically reshaping the neuronal methylome. Asymmetric enrichment of hmC on the sense strand of actively transcribed genes increases in a linear, clock-like fashion throughout the lifespan, indicating a mechanistic link between transcription and hmC. We found that sex differences in X-linked DNA methylation in the human brain are primarily driven by hmCG rather than mCG, suggesting an important role for hmC in X-chromosome inactivation (XCI) and escape gene expression. We found key changes in 5hmC at dynamic cis-regulatory elements marked by changing cell type-specific levels of active and repressive histone modifications. Collectively, our findings reveal the dynamic trajectory of hmC in human neurons across the lifespan and highlight the association of DNA hydroxymethylation with transcription, chromatin state, and sex-specific gene regulation.

GSE330007 Transcriptomic Analysis Reveals Molecular Signatures Distinguishing Vocal Fold Leukoplakia from Benign Lesions: Synergistic Dysregulation of Chronic Inflammation, Immune Dysfunction, and Epithelial Barrier Disruption

Sun, 10 May 2026 00:00:00 -0400

Contributors : Zhixian Xiao ; Li Zhou ; Xiaocui Long ; Li Tian ; Xing Li
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Objective: Vocal cord leukoplakia (VCL) represents a precancerous laryngeal lesion with a risk of malignant transformation. By employing transcriptomic analysis, this research sought to ascertain the key signatures and regulatory networks capable of distinguishing VCL from benign lesions. Methods: Surgically resected tissues from 8 individuals with VCL and 11 individuals with vocal cord polyps (VCP) were included for RNA sequencing and bioinformatics analysis. Core genes were identified through differential expression analysis, and functional enrichment analyses were utilized to characterize the associated biological processes. Results: The transcriptomic profile of VCL was characterized by abnormalities in three primary aspects: activation of inflammation-related pathways (e.g., NF-κB), downregulation of immune function-related genes (e.g., CD8A, CD19), and downregulation of epithelial barrier-related molecules (e.g., CLDN4). Conclusion: The transcriptomic signatures of VCL are linked to the coordinated dysregulation of pathways related to inflammation, immunity, and the epithelial barrier.

GSE329979 Spatiotemporal Role of GLI2 in Driving SHH-Medulloblastoma Tumorigenesis

Sun, 10 May 2026 00:00:00 -0400

Contributors : Samuel Rivero-Hinojosa ; Najiba Murad
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Medulloblastoma (MB) is a malignant cerebellar tumor primarily affecting children. SHH MB with GLI2 amplification is associated with a particularly poor prognosis. Although GLI2 amplification is clinically recognized, its role in driving SHH-MB remains unclear. We generated novel mouse models of GLI2-amplified MB to investigate the role of GLI2 in driving tumorigenesis and assessed their similarity to human tumors using immunohistological and scRNA-seq analyses. Additionally, we examined the spatiotemporal window of tumor development using our mouse models and explored the mechanisms underlying the susceptibility of embryonic cerebellar granule cell progenitors (GCPs) to GLI2-induced tumorigenesis through scRNA-seq analysis. We further investigated the involvement of MAPK pathway in GLI2-driven tumorigenesis and progression by genetically disrupting the pathway. We demonstrate that GLI2 is a primary oncogenic driver in SHH-MB, with its overexpression driving embryonic Math1+ progenitor cells to form SHH-MB. The resulting GLI2-driven tumors closely resemble human GLI2-amplified SHH-MB cellularly and molecularly. Additionally, we determined that embryonic Math1+ GCPs at E13.5–E15.5 are the most susceptible to tumor initiation with GLI2 overexpression alone. In postnatal Math1+ GCPs, additional Trp53 inactivation is required for GLI2-induced tumor formation. scRNA-seq analysis reveals MAPK pathway enrichment in embryonic GCPs and GLI2-driven tumors. Functional studies show that knocking down MEK1/2 in Math1+ progenitor cells or GLI2-driven MB cells prevents tumorigenesis and tumor progression, respectively. Our studies uncover the developmental origins and molecular mechanisms underlying GLI2-amplified SHH-MB. We also reveal that the MAPK pathway plays a critical role in GLI2-driven SHH-MB tumorigenesis and progression.

GSE329959 Diversity and evolution of chromatin regulatory states across eukaryotes [ChIP-Seq]

Sun, 10 May 2026 00:00:00 -0400

Contributors : Arnau Sebe-Pedros ; Cristina Navarrete ; Sean A Montgomery
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Acanthamoeba castellanii ; Arabidopsis thaliana ; Bigelowiella natans ; Creolimax fragrantissima ; Dictyostelium discoideum ; Guillardia theta ; Naegleria gruberi ; Nematostella vectensis ; Physcomitrium patens ; Saccharomyces cerevisiae ; Spizellomyces punctatus ; Tetrahymena thermophila

Histone post-translational modifications (hPTMs) are key regulators of chromatin states, influencing gene expression, epigenetic memory, and transposable element repression across eukaryotic genomes. While many hPTMs are evolutionarily conserved, the extent to which the chromatin states they define are similarly preserved remains unclear. Here, we developed a combinatorial indexing ChIP-seq method to simultaneously profile specific hPTMs across diverse eukaryotic lineages, including amoebozoans, rhizarians, discobans, and cryptomonads. Our analyses revealed highly conserved euchromatin states at active gene promoters and gene bodies. In contrast, we observed diverse configurations of repressive heterochromatin states associated with silenced genes and transposable elements, characterized by various combinations of hPTMs such as H3K9me3, H3K27me3 and/or different H3K79 methylations. These findings suggest that while core hPTMs are ancient and broadly conserved, their functional readout has diversified throughout eukaryotic evolution, shaping lineage-specific chromatin landscapes.

GSE329952 Diversity and evolution of chromatin regulatory states across eukaryotes

Sun, 10 May 2026 00:00:00 -0400

Contributors : Arnau Sebe-Pedros ; Cristina Navarrete ; Sean A Montgomery
Series Type : Expression profiling by high throughput sequencing
Organism : Acanthamoeba castellanii ; Arabidopsis thaliana ; Bigelowiella natans ; Creolimax fragrantissima ; Dictyostelium discoideum ; Guillardia theta ; Naegleria gruberi ; Nematostella vectensis ; Physcomitrium patens ; Saccharomyces cerevisiae ; Spizellomyces punctatus ; Tetrahymena thermophila

GSE329834 Genetic interaction analysis of PIH1 deletion strains (GIM screen)

Sun, 10 May 2026 00:00:00 -0400

Contributor : Cosmin Saveanu
Series Type : Genome variation profiling by array
Organism : Saccharomyces cerevisiae ; Saccharomyces cerevisiae S288C

A S. cerevisiae strain with deletion of the PIH1 gene was combined with two collections of yeast mutants: one in which non-essential genes were deleted and one in which an long 3' UTR extension has been added to the mRNA of essential genes (GIM method, Decourty et al., 2008). Combined double-mutant deletion cells growth was quantified using barcodes that are specific for each gene mutation. A reference population was obtained by mixing the results of 15 GIM screens DNA prior to barcode amplification and labeling (Decourty et al., NAR 2021).

GSE329625 A deep cellular atlas of the human ventral substantia nigra in Parkinson's identifies a genetic and molecular overlap with insulin resistance

Sun, 10 May 2026 00:00:00 -0400

Contributors : Viola Volpato ; David Menassa ; Preethi Sheshadri ; Stefania Giussani ; Michal Rokicki ; Lucia Cardo ; Marirena Bafaloukou ; Ann-Kathryn Schalkamp ; Agata Zaremba ; Jimena Monzón-Sandoval ; Ngoc-Nga Vinh ; Joanne Morgan ; Michele Hu ; Scott Miners ; Richard Wade-Martins ; Cynthia Sandor ; Laura Parkkinen ; Caleb Webber
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Parkinson’s disease (PD) is a complex neurodegenerative disorder characterised by selective neuronal loss. We integrate deep full-length single-nuclei sequencing of the human substantia nigra with novel genome-wide association studies (GWAS) identifying genetic and cellular drivers of PD. Genetic risk converges on AGTR1+ dopaminergic neurons and perineuronal oligodendrocytes (pODCs), both reduced in PD, as well as oligodendrocyte precursor cells, enriched among disease-disrupted intercellular interactions. AGTR1+ neurons represent a metabolically stressed state, characterised by renin-angiotensin system (RAS) and MAPK activation, oxidative stress, and mitochondrial dysfunction, rather than a distinct subtype. AGTR1+ neurons and pODCs link PD risk to metabolic traits; in pODCs, this association reflects insulin resistance with downregulated PI3K–AKT signalling.

GSE329623 Integrated single-cell RNA sequencing and untargeted metabolomics reveals β-elemene’s immune and metabolic modulation in triple-negative breast cancer

Sun, 10 May 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Triple-negative breast cancer (TNBC) presents a significant challenge in women’s health due to its aggressive phenotype and the absence of targeted therapeutic options. β-Elemene, a sesquiterpene isolated from Curcuma wenyujin, has demonstrated clinical benefits against TNBC; however, its mechanisms of action, particularly with respect to the immune and metabolic tumor microenvironment, remain poorly characterized. In this study, we employed single-cell RNA sequencing and untargeted metabolomics to investigate how β-elemene reshapes the cellular and metabolic landscape of TNBC using a 4T1 orthotopic mouse model. Our findings are expected to provide the first comprehensive elucidation of β-elemene’s dual immunomodulatory and metabolic effects in TNBC, highlighting the potential of natural compounds to enhance antitumor immunity.

GSE329279 In Vitro Single-Cell Transcriptomic Profiling of Cultured SCAP and DPSCs: Unveiling Cellular Heterogeneity

Sun, 10 May 2026 00:00:00 -0400

Contributors : Maanas Shah ; Mohamed Al Sayegh ; Mennatullah Khalil ; Mano Sundarabupathi ; Omer AlKhnbashi ; Costerwell Khyriem ; Lakshman Samaranayake ; Mehar Sultana ; Hiroshi Egusa ; Mohamed Jamal
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Abstract: Introduction: Dental-derived mesenchymal stem cells show considerable variability in their differentiation potential, due to use of non-specific surface markers and technical limitations in isolation protocols. This study aimed to employ single-cell RNA sequencing to compare the cellular composition of cultured stem cells from apical papilla (SCAPs) and dental pulp (DPSCs), with the goal of detecting subpopulations underlying their divergent regenerative behavior and identify markers that can facilitate future isolation and functional targeting. Methodology: SCAP and DPSC tissues were obtained from three human donors and cultured to passage 2. Single-cell suspensions were sequenced to generate gene expression profiles. Dimensionality reduction and clustering were performed using the Seurat package and visualized via UMAP. Cluster-specific differential gene expression was computed as log2fold change, followed by gene set enrichment analysis. Pseudotime trajectory analysis was used to map lineage progression based on transcriptional gene expression. Results: Transcriptomic analysis identified 12 distinct clusters shared across DPSC and SCAP cultures. While both cell types contributed comparably to overall biological processes, key differences emerged within specific clusters. Clusters 3, 4, 5, 6, and 9 expressed high levels of proliferative markers (MKI67, TOP2A, TYMS), suggesting active proliferating populations. Cluster 9 was notable for the co-expression of pericyte-associated markers (NOTCH3, PDGFRB) alongside canonical MSC markers (MCAM, THY1, DCN), identifying a previously uncharacterized progenitor-like subset. NOTCH3 and PDGFRB were also present in a more mature fibroblast-enriched population in cluster 7, dominated by collagen-related genes. IGFBP3 and IGFBP5 were selectively enriched in SCAP-derived clusters 7 and 9, whereas IGFBP4, 6, and 7 were expressed across both DPSC and SCAP populations. Clusters 10 and 11, primarily derived from DPSCs, were enriched in stress-response, heat shock, and apoptotic genes, which may reflect culture-induced adaptations. Pseudotime trajectory inference positioned cluster 9 at a putative progenitor-like node; however, this represents a hypothesis-generating model based on transcriptional similarity in cultured cells rather than validated lineage relationships. Conclusion: This study provides a high-resolution single-cell transcriptomic comparison of cultured SCAPs and DPSCs, revealing distinct transcriptional profiles and cellular heterogeneity. SCAPs may harbor a broader spectrum of proliferative progenitors under these culture conditions, particularly in clusters 7 and 9, enriched in IGF-, PDGFRB-, and NOTCH-associated genes. These findings generate testable hypotheses regarding subpopulation-specific regenerative roles. Future studies using prospective isolation based on NOTCH3/PDGFRB and functional in vitro and in vivo validation are needed to establish their regenerative potential and translational relevance.

GSE327921 Targeting PDE2A of macrophages attenuates sorafenib-induced cardiotoxicity

Sun, 10 May 2026 00:00:00 -0400

Contributors : Sijia Li ; Shuangli Zhu ; Kai Fu ; Can Pan ; Yuelu Lan ; Xueping Wang ; Xin Su ; Zhangqi Cao ; Fang Wang ; Liwu Fu
Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

Background: Sorafenib, a multi-kinase inhibitor widely used in hepatocellular carcinoma, is associated with clinically relevant cardiotoxicity, but the underlying mechanisms remain incompletely understood. Cardiac macrophages are key regulators of inflammatory injury in the heart; however, their role in sorafenib-induced cardiotoxicity (SIC) has not been fully defined. Methods: A murine model of SIC was established in C57BL/6J mice. Indirect macrophage-cardiomyocyte co-culture systems were used for in vitro mechanistic studies. Macrophages were depleted in vivo using PLX3397. Transcriptomic profiling was performed to identify candidate mediators associated with macrophage-related SIC. PDE2A was further investigated using genetic knockdown and pharmacological inhibition in cellular and animal models. Results: Sorafenib induced cardiac dysfunction, myocardial injury, and inflammatory remodeling in vivo, accompanied by increased cardiac macrophage infiltration and a shift toward a pro-inflammatory phenotype. In vitro, macrophages exacerbated sorafenib-induced cardiomyocyte injury, oxidative stress, and mitochondrial dysfunction, whereas macrophage depletion attenuated SIC in vivo. Transcriptomic analysis identified PDE2A as an upregulated candidate in sorafenib-injured hearts, and this increase was reduced by macrophage depletion. PDE2A expression was preferentially increased in macrophages rather than cardiomyocytes under sorafenib exposure. Genetic or pharmacological inhibition of PDE2A attenuated injury-related phenotypes and inflammatory activation in vitro and alleviated SIC in vivo. Mechanistically, these effects were predominantly associated with cGMP/PKG signaling rather than cAMP/PKA signaling. In tumor-bearing models, BAY60-7550 did not compromise the anti-tumor effect of sorafenib and was associated with enhanced tumor suppression. Conclusion: These findings indicate that sorafenib-induced cardiotoxicity is closely associated with macrophage-driven inflammatory remodeling and identify PDE2A as a candidate mediator of this process. Pharmacological inhibition of PDE2A attenuated cardiac injury while maintaining, and potentially enhancing, the anti-tumor activity of sorafenib, supporting PDE2A as a potential therapeutic target in this setting.

GSE302088 Inhibition of Acetyl-CoA-carboxylase induces endoplasmic reticulum stress and has synergistic effects with anti-cancer therapies

Sun, 10 May 2026 00:00:00 -0400

Contributors : Shan Naing Lin ; Dai Jiawei ; Wang Yueyue ; Pusztai Lajos
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Background: Acetyle-CoA-carboxylase-1 (ACC1) is overexpressed in many cancer types relative to normal tissues and catalyzes the rate limiting step of de novo fatty acid synthesis. In this study, we identified a new downstream effect of ACC inhibition and demonstrate synergy between a small molecule inhibitor of ACC, PF0517515, and clinically used anti-cancer agents. Methods: High throughput cell line (N=300 10 cell lines) and combinatorial drug screens (n=166 FDA-approved drugs) were performed along with in vivo mice xenograft experiments. We analyzed bulk and single cell RNA sequencing, and lipid profiling results of PF0517515 treated cells, and performed western blot analysis of endoplasmic reticulum stress proteins to elucidate cellular effects of ACC inhibition. Results: Single agent PF-05175157 inhibited the growth of several different cancer types, myeloma, ovarian, lung and breast cancer cells resistant to various targeted therapies. PF-05175157 augmented the anti-cancer efficacy of a range of drugs including tyrosine kinase inhibitors and chemotherapy agents. Synergy with doxorubicin and vinorelbine were also demonstrated in mice xenografts. In breast cancer cells, ACC inhibition increased the protein (and mRNA) expression levels of genes involved in endoplasmic reticulum stress and unfolded protein response including a rapid increase in phospho-IRE1 by 6h, and more gradual increase in phospho-EIF2, ATF4, and ATF6 expressions by 24h and 72h. Lipid profiling after 48h exposure to drug showed decrease in many membrane components including c14:0/c16:0 and c16:0/c18:1 that facilitate membrane protein integration. There was an increase in unsaturated long-chain fatty acids and an increase in 4-Hydroxynonenal and 4-Hydroxyhexenal indicating increased lipid peroxidation. Single cell RNA sequencing showed large scale metabolic slowdown with decreased oxidative phosphorylation, amino acid and steroid biosynthesis, glutathione-, carbon-, pyruvate-, and purine-metabolism. Pathways of ferroptosis, reactive oxygen, sphingolipid, steroid hormone and folate biosynthesis were upregulated suggesting response to oxidative stress and compensatory lipid synthesis. Seven-day post-recovery cells compared to pretreatment, continued to show downregulation of proteasome, spliceosome, amino acid synthesis, DNA replication/DNA repair, cell cycle, oxidative phosphorylation, and glycolysis /gluconeogenesis indicating less than full metabolic recovery. Conclusion: PF-05175157 alters cellular lipid composition, induces endoplasmic reticulum stress, and shows broad synergy with various anti-cancer therapies in vitro and in vivo.

GSE298095 Inducible fusion with the CHASERR long noncoding RNA transcript upregulates haploinsufficient CHD2 expression

Sun, 10 May 2026 00:00:00 -0400

Contributor : Igor Ulitsky
Series Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens ; Mus musculus

Long noncoding RNAs are now realized to function in various biological processes via multiple, and as of yet not fully understood, modes of action. CHASERR is a long noncoding RNA conserved throughout vertebrates, located immediately upstream of the promoter of the CHD2 gene. CHD2 haploinsufficiency leads to a neurodevelopmental disorder that includes epilepsy and intellectual disability. Homozygous loss of CHASERR promoter leads to embryonic lethality in mice, and heterozygous deletions lead to pleiotropic phenotypes in mice and a recently characterized syndromic human developmental disorder. Short highly conserved sequence motifs are present in the last exon of CHASERR and blocking them with antisense oligonucleotides (ASOs) up-regulates CHD2 expression. Here, we decipher the mechanism of action of these ASOs and show that they stimulate the formation of a fusion transcript connecting the first four exons of CHASERR with exons 2–39 of CHD2. These fusion transcripts are exported to the cytoplasm and translated to produce full-length CHD2 proteins. They are expressed endogenously, albeit at low levels, and are induced in activated neurons. Deletion of these conserved regions in mice mimics the effects of the ASO, leading to increased CHD2 levels, altered chromatin accessibility and altered neuronal responses. Perinatal introduction of the ASO into the brains of Chd2+/– mice up-regulates CHD2 expression and alleviates behavioral phenotypes caused by CHD2 haploinsufficiency, providing a therapeutic route to CHD2 haploinsufficiency. The concept of targeting upstream genes with ASOs to induce transcript fusion can be extended to other gene pairs.

GSE296418 Gene expression profiling of HDAC inhibitor-resistant and parental cutaneous T-cell lymphoma cell lines

Sun, 10 May 2026 00:00:00 -0400

Contributors : Yuto Takahashi ; Akihiro Kitadate
Series Type : Expression profiling by array
Organism : Homo sapiens

Comprehensive transcriptome analysis was conducted to identify genes associated with HDAC inhibitor resistance in cutaneous T-cell lymphoma. A set of 83 genes was found to be commonly upregulated (fold change > 2.5) in both resistant cell lines.

GSE292598 YAPTAZ and neuroblastoma cell plasticity [RNA-Seq]

Sun, 10 May 2026 00:00:00 -0400

Contributors : Cécile Thirant ; Isabelle Janoueix-Lerosey
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

Spontaneous and reversible plasticity between two tumor cell states, noradrenergic and mesenchymal, has been described in neuroblastoma cell lines. Here, we show that YAP, TAZ, and their target genes are marked by super-enhancers and are strongly and specifically expressed in mesenchymal tumor cells. We characterize a core regulatory circuitry containing YAP/TAZ, TEAD, FOSL and RUNX factors that controls gene expression linked to a mesenchymal identity in neuroblastoma. Genetic or pharmacological inactivation of YAP/TAZ reduces cell proliferation of mesenchymal neuroblastoma cells. The expression of a YAP/TAZ gene signature fully correlates with a mesenchymal identity in several models exhibiting plasticity between noradrenergic and mesenchymal states. Whereas YAP/TAZ inhibition impairs the noradrenergic to mesenchymal transition, YAP and/or TAZ overexpression induces a mesenchymal shift traduced by transcriptional and functional reprogramming, accompanied by the repression of noradrenergic identity. Altogether, these findings uncover a neuroblastoma-specific YAP/TAZ core regulatory circuitry controlling the switch of cell state towards a mesenchymal identity in neuroblastoma.

GSE292597 YAPTAZ and neuroblastoma cell plasticity [ChIP-seq]

Sun, 10 May 2026 00:00:00 -0400

Contributors : Cécile Thirant ; Isabelle Janoueix-Lerosey
Series Type : Genome binding/occupancy profiling by high throughput sequencing
Organism : Homo sapiens

High-risk neuroblastoma is a pediatric malignancy marked by poor prognosis, high metastatic potential, and resistance to conventional therapies. Phenotypic plasticity between noradrenergic and mesenchymal cell states, each defined by specific transcriptional and epigenetic programs and distinct cellular properties, is observed in some neuroblastoma cell lines. Yet the drivers of this plasticity are not fully understood. This study identifies YAP and TAZ as central regulators of the mesenchymal state. YAP/TAZ, in complex with TEAD, FOSL, and RUNX transcription factors, establish a core regulatory circuitry associated with mesenchymal-specific super-enhancers. Expression of a conserved YAP/TAZ gene signature increases during the noradrenergic-to-mesenchymal transition and decreases during the reverse in plasticity models. Genetic or pharmacological inactivation of YAP/TAZ abrogates cellular proliferation and inhibits the noradrenergic-to-mesenchymal transition. Conversely, overexpression of YAP/TAZ in noradrenergic cells induces a major transcriptional reprogramming towards a mesenchymal state, via a redistribution of TEAD4 and a rewiring of the epigenetic landscape. These findings uncover a YAP/TAZ-TEAD4 driven epigenetic mechanism underlying tumor cell plasticity in neuroblastoma.

GSE292595 YAPTAZ and neuroblastoma cell plasticity [scRNA-Seq]

Sun, 10 May 2026 00:00:00 -0400

Contributors : Cécile Thirant ; Isabelle Janoueix-Lerosey
Series Type : Expression profiling by high throughput sequencing
Organism : Homo sapiens

GSE292245 Interleukin-34-dependent perivascular macrophages promote vascular function in the brain

Sun, 10 May 2026 00:00:00 -0400

Series Type : Expression profiling by high throughput sequencing
Organism : Mus musculus

The development of most macrophages depends on the colony-stimulating factor 1 (CSF-1) receptor, which has two ligands: CSF-1 and interleukin-34 (IL-34). While IL-34 is required for the homeostasis of microglia, the parenchymal macrophages in the central nervous system (CNS), it is unclear whether brain border-associated macrophages (BAMs) also depend on this cytokine. Here, we demonstrated that the embryonic development of murine BAMs in the choroid plexus, leptomeninges, and perivascular spaces required CSF-1, while IL-34 was critical for their maintenance in adulthood. In the brain, Il34 was expressed by mural cells and perivascular fibroblasts, and its transgenic deletion in these cells interrupted BAM maintenance. Il34-deficiency coincided with transcriptional changes in vascular cells, leading to increased flow velocity and vasomotion in pial and penetrating arterioles. Similarly, Mrc1CreCsf1rfl/fl mice lacking CD206+ perivascular BAMs exhibited increased hemodynamics in arterial networks. These findings reveal a crosstalk between vascular cells and CNS macrophages regulating cerebrovascular function.