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DeCAF defines clinical fibroblast subtypes and multidimensional tumor-stroma crosstalk shaping prognosis and immunotherapy response
Single-cell RNA sequencing (scRNA-seq) studies have uncovered distinct cancer-associated fibroblast (CAF) populations. While useful as a biological framework, no studies have conclusively defined CAF subtypes with clinical significance. We define restraining (rest) and promoting (pro) …
Read PDFPACLseq: A Standalone Diagnostic Method for Ph-Like Acute Lymphoblastic Leukemia Using Nanopore Sequencing
Timely and accurate detection of Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL)-related fusion gene is essential for treatment decisions. However, due to the complexity of possible gene fusion combinations of Ph-like ALL, current diagnostic workflows …
Read PDFPatient-derived induced pluripotent stem cells with a C9orf72 expansion as a model to study frontotemporal dementia pathologies
The neurodegenerative disorder frontotemporal dementia (FTD) can be caused by a repeat expansion (GGGGCC; G4C2) in C9orf72. The function of wild-type C9orf72 and the mechanism by which the C9orf72-G4C2 expansion causes FTD, however, remain unresolved. …
Read PDFDeep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrotic remodeling of the skin and internal organs. Fibrotic tissue changes are considered hardly reversible with current therapies, suggesting that new strategies are required …
Read PDFLoss of polarity by Cdc42 depletion and oncogenic Kras activation in the mouse intestinal epithelia leads to a necrotizing enterocolitis (NEC)-like disease
Cell polarity is essential for maintaining intestinal epithelial organization and function. Here we show that combined loss of polarity by epithelial loss of Cdc42 with oncogenic Kras expression in mice causes small intestine failure leading …
Read PDFProbing the limits of genetic recoding using multi-omics-guided evolution
Engineering the genetic code-by reassigning multiple of the 64 natural codons-enables making organisms resistant to all viruses, preventing genetic information exchange, and allowing the biosynthesis of genetically encoded unnatural polymers. However, synonymous codon replacement-recoding-is frequently …
Read PDFSmall RNA sequencing datasets from caryopses and flag leaves of multiple rice genotypes exposed to high nighttime temperature stress
The increasing frequency and severity of High Nighttime Temperature (HNT) threatens to damage rice quality by inducing the chalky grain phenotype. To better understand the roles that small RNAs (sRNAs) play in HNT-induced chalkiness in …
Read PDFTumor microenvironment transcriptional activity enables robust stratification of chemotherapy response in triple-negative breast cancer
Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA …
Read PDFAn Integrative ATAC-Seq and RNA-Seq Analysis of Spleen Tissues from Largemouth Bass (<i>Micropterus salmoides</i>) Infected with Iridovirus (LMBV)
In this study, we systematically analyzed the dynamic changes in chromatin accessibility and the transcriptional responses in the spleen of largemouth bass (<i>Micropterus salmoides</i>) following infection with iridovirus (LMBV) using the assay for transposase-accessible chromatin …
Read PDFZBTB18-mediated STAT1 transcriptional repression contributes to bovine myogenesis, implying an association with oxidative myofiber formation and beef eating quality
Skeletal muscle development, orchestrated by muscle stem cells (MuSCs), is a critical determinant of meat yield and quality in cattle. Transcription factors (TFs) are pivotal regulators of MuSCs fate, yet their specific roles in meat …
Read PDFInflammatory monocytes constrain YAP-induced cell proliferation
<i>YAP</i> and its paralog, <i>TAZ</i>, are transcriptional coactivators of the Hippo pathway that regulate cell growth. Their structural distinctiveness suggests important independent functional differences. To investigate this further, we generated YAP- and TAZ-predominant clones in …
Read PDFNonsense-mediated mRNA decay factors target short poly(A)-tailed mRNAs lacking a premature termination codon
Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway known to degrade mRNAs containing premature termination codons (PTCs). mRNA recognition by the Upf1, Upf2 and Upf3 NMD factors is favoured by long distances between …
Read PDFHarnessing toxin-mediated ribosome stalling as a complementary tool to annotate bacterial ORFs
The Mycobacterium tuberculosis (Mtb) VapC4 endoribonuclease toxin exclusively cleaves and inactivates tRNACys, which leads to extensive ribosome stalling at Cys codons. Serendipitously, the precise position of stalled ribosomes is revealed within our 5' RNA-seq datasets …
Read PDFMajor transitions in early coral development: novel insights enabled by visualisation of a comprehensive transcriptomic dataset for Acropora millepora
<h4>Background</h4>Given the ecological importance of reef-building corals (Scleractinia), it is perhaps surprising that the molecular mechanisms underlying many of the morphological and metabolic changes during their development remain unclear. In part, this is due to …
Read PDFVirulence gains in the Puccinia striiformis f. sp. tritici PstS10 lineage correlate with expression polymorphism in a candidate Avr effector
Wheat yellow rust - caused by Puccinia striiformis f. sp. tritici (Pst) - is the most damaging wheat rust in Europe, where three distinct races (Kalmar, Amboise and Benchmark) recently became prevalent. Herein, comparative genomic …
Read PDFT-bet Fate Mapping Reveals Gestational Stage-Specific Transcriptional Adaptation of Decidual NK Cells
<h4>Problem</h4>Natural killer (NK) cells are critical regulators of immune balance at the maternal-fetal interface. T-bet (Tbx21) is a key transcription factor shaping NK cell effector functions, yet its role in decidual NK (dNK) cell adaptation …
Read PDFDe novo transcriptome assembly of Clitoria ternatea flowers
<h4>Objective</h4>The Clitoria ternate flowers are widely used for its anthocyanin pigmentation. However, the flowers' colour ranges from white to light blue to deep blue, purple or even pink. The butterfly pea flower colours are known …
Read PDFYAP1 and QSER1 are key modulators of embryonic signaling pathways in the mammalian epiblast
YAP1 signaling is essential for development but its specific roles in early embryogenesis remain poorly understood. To shed light on this, we analyze YAP1's role in regulating the pluripotency of the mammalian epiblast, using scRNAseq …
Read PDFSize-Modulated Mesoderm-Endoderm Divergence and Myocardial Cavitation in Micropatterned Cardioids
The human heart, originating from the splanchnic mesoderm, is the first functional organ to develop, co-evolving with the foregut endoderm through reciprocal signaling. Previously, cardioid models offered new insights on cardiovascular cell lineages and tissue …
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