Publications by authors named "Akinori Kanai"
The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses.
View Article and Find Full Text PDFTendons and ligaments are crucial connective tissues linking bones and muscles, yet achieving full functional recovery after injury remains challenging. We investigated the characteristics of tendon stem/progenitor cells (TSPCs) by focusing on the declining tendon repair capacity with growth. Using single-cell RNA sequencing on Achilles tendon cells from 2- and 6-week-old mice, we identified and as novel surface antigen markers for TSPCs.
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- Age at exposure significantly influences the risk of developing cancer from radiation, yet how age impacts this process is not fully understood.
- This study compares the DNA damage responses between two types of intestinal stem cells in mice, focusing on differences between adult and infant cells after radiation exposure.
- Results showed that adult Lgr5- stem cells are more affected by radiation than Lgr5+ cells, and infants display distinct cellular responses, suggesting that age affects how stem cells respond to radiation damage, which may explain varying cancer risks.
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- The genome faces constant DNA damage from both internal and external sources, requiring precise regulation of repair mechanisms to maintain integrity.
- After exposure to ionizing radiation (IR), the modification of histone H3 (H3K4me3) shows a decrease shortly after and an increase later, indicating the dynamic response of chromatin to DNA damage in both human and mouse cells.
- PTIP, a critical component of a histone methyltransferase complex, is necessary for the upregulation of H3K4me3 and helps induce cell cycle arrest by activating the PRDM1 cell cycle inhibitor, with its reduced expression linked to acute myeloid leukemia.
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- Cerebral small vessel disease (cSVD) is a major contributor to stroke and dementia, and currently lacks specific treatments, prompting a study using Mendelian randomization to identify protein associations.
- The research combined cerebrospinal fluid (CSF) and plasma data with genetic studies to identify 49 proteins linked to cSVD, highlighting 16 that appeared in both fluids and showing connections to immune response and extracellular matrix pathways.
- Notably, many identified proteins were associated with stroke and dementia, with some already having known drug targets, paving the way for potential new biomarkers and therapies for cSVD.
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- Acetylation of histones by lysine acetyltransferases (KATs) plays a crucial role in regulating chromatin structure and gene expression.* -
- The study highlights how the winged helix domain of human MORF KAT can simultaneously bind to both the TAZ2 domain of p300 KAT and specific DNA sequences.* -
- Findings indicate that MORF and p300 KATs work together to enhance transcriptional regulation at gene promoters enriched in CpG sequences.*
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- JADE is a key part of the HBO1 acetyltransferase complex, which plays a significant role in regulating gene transcription and developmental processes.
- The PZP domain of JADE binds to histone H3 and DNA, facilitating the recruitment of the HBO1 complex to chromatin and influencing its enzymatic activity based on the methylation status of H3K4.
- JADE’s involvement is linked to leukemogenesis, enhancing the activity of specific fusion proteins, indicating its critical role in both normal and pathological cellular functions.
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- The study investigates the early stages of tumor development, specifically focusing on lung adenocarcinomas like adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma.
- Researchers conducted comprehensive genomic analysis on 76 lung cancer samples, combining sequencing data with transcriptomic and epigenomic information.
- Findings indicate that very early-stage tumors have minimal somatic mutations, primarily in key driver mutations, leading to copy number changes and global DNA hypomethylation as the disease progresses, particularly in Noguchi type B tumors.
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- ATP-dependent chromatin remodeling complexes, specifically non-canonical BAF (ncBAF), play important roles in hematopoietic stem cells (HSCs), but their functions haven't been fully explored.* -
- The study focuses on BRD9, a key component of ncBAF, finding that its loss increases chromatin accessibility, leading to a preference for myeloid cell development while hindering B cell formation.* -
- BRD9 is shown to interact with CTCF, which affects gene expression and chromatin structure in HSCs, highlighting ncBAF's crucial role in determining cell fate in both normal and cancerous blood cell development.*
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- * Multiomics analysis showed MNKPL is distinct from other leukemia types and suggested that both NK and myeloid cells may originate from shared progenitor cells.
- * Current treatments for MNKPL are not very effective, but the study found that MNKPL is especially sensitive to the drug l-asparaginase, which aligns with clinical observations of its effectiveness in patients.
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- * Key genes related to NMJ formation, including Dok7, Chrna1, and Chrnd, were found to be expressed in myonuclei at a critical stage of embryonic development (E18.5), with around 10.7% of myonuclei expressing these genes alongside regulators like Amotl2 and Ptprk.
- * Distinct roles were identified for various β-catenin regulators, where Amotl2 and Ptprk were crucial for NMJ structural organization, while Fam53b
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- Cancer stem cells (CSCs) show diversity within tumors, making it hard to target treatments effectively, especially in triple-negative breast cancer (TNBC).
- Through single-cell transcriptomics, researchers identified a specific subpopulation of CSCs characterized by FXYD3, which is linked to drug resistance during chemotherapy.
- Targeting the Na+/K+ pump with specific inhibitors, such as cardiac glycosides, could potentially improve treatment outcomes by eliminating these resistant CSCs, leading to better TNBC patient prognoses.
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- * Myeloma cells release specific microRNAs (miR-106a-5p and miR-146a-5p) via exosomes, which enhance the induction of suppressive immune cells called M-MDSCs from healthy blood cells.
- * These microRNAs work alongside other factors like CCL5 and MIF to upregulate molecules that contribute to immune suppression, suggesting new therapeutic approaches to improve immunotherapy effectiveness in MM.
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- * Long-term use of stimulants to maintain their function can have undesirable side effects, making PPARα a better target for preserving beige adipocytes.
- * Pemafibrate, a medication used for treating dyslipidemia, has been shown to enhance the thermogenic ability of these cells, reduce body weight gain, and improve glucose tolerance in obese mouse models.
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- Aberrant immune signaling in hematopoietic stem/progenitor cells (HSPCs) plays a significant role in the development of myelodysplastic syndrome (MDS).
- A study showed that prior stimulation with bacterial and viral products, combined with the loss of the Tet2 gene, activated certain genes through Elf1, impacting the stem cells' epigenome without increasing mutations.
- Inhibiting Polo-like kinases (Plk) or knocking down Elf1 can reverse these changes in stem cells, which correlates with findings that this Elf1-related signature is prevalent in human MDS HSPCs.
Changes in the transcriptional machinery cause aberrant self-renewal of non-stem hematopoietic progenitors. AF10 fusions, such as CALM-AF10, are generated via chromosomal translocations, causing malignant leukemia. In this study, we demonstrate that AF10 fusion proteins cause aberrant self-renewal via ENL, which binds to MOZ/MORF lysine acetyltransferases (KATs).
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- * DDX41 is an RNA helicase critical for RNA metabolism and ribosome biogenesis, impacting the processing of pre-ribosomal RNA.
- * Research using ribosome profiling revealed that reducing DDX41 levels affects the translation of various transcripts, suggesting a feedback mechanism that regulates ribosome biogenesis based on DDX41 activity.
Article Synopsis
- Human acetyltransferases MOZ and MORF play a role in aggressive leukemias due to chromosomal translocations involving their amino terminus, but the specifics of this function were unclear.
- Researchers identified two winged helix (WH) domains in both MOZ and MORF, which bind to DNA—particularly unmethylated CpG sequences—and promote gene transcription through H3K23 acetylation.
- Advanced studies (like Cryo-EM and mass spectrometry) revealed the DNA-binding mechanisms of these domains, suggesting potential therapeutic approaches for diseases linked to abnormal MOZ/MORF activities.
Myeloid malignancies with DDX41 mutations are often associated with bone marrow failure and cytopenia before overt disease manifestation. However, the mechanisms underlying these specific conditions remain elusive. Here, we demonstrate that loss of DDX41 function impairs efficient RNA splicing, resulting in DNA replication stress with excess R-loop formation.
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- - KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) is a challenging type of childhood leukemia, and researchers conducted extensive genetic studies on 84 infants with this condition to understand its complexity.
- - The analysis revealed five distinct clusters of the disease, each characterized by different genetic factors and stages of blood cell development, which include various types of IRX and HOXA gene involvement.
- - A key finding is that specific mutations in the RAS pathway can predict patient outcomes, with one subgroup showing a high mutation rate and severe prognosis, emphasizing the need for personalized treatment strategies based on genetic insights.
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- Scientists found special helpers called enhancers that help some animals regrow body parts, but they didn't know how they worked.
- They studied kidney tubes in these animals to figure out which genes the enhancers control using advanced lab techniques.
- They discovered that a gene called Klf15 is really important for helping these kidney tubes regenerate, and blocking it stops the regeneration from happening.
Background: Histologic tumor necrosis (TN) is a well-established independent prognostic indicator in patients treated surgically for clear cell renal cell carcinoma (ccRCC). However, the precise mechanisms by which TN alters disease progression remain unknown. The DEAD-box protein DDX41, a member of a large family of helicases, has been characterized as a pattern recognition receptor against an array of double-stranded (ds)DNA produced from bacteria, dsDNA viruses, and nearby cells that have released dsDNA fragments through necrosis.
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- Researchers analyzed non-small cell lung cancer from 20 Japanese patients using a combination of short and long read sequencing, achieving long phased DNA segments with high accuracy.
- The study found that mutations in cancer genomes are not evenly spread across both chromosome copies, with large chromosomal rearrangements occurring more frequently on one chromosome, particularly in EGFR mutation-positive lung adenocarcinomas.
- The integration of epigenomic and transcriptomic data indicated that the two copies of chromosomes can have different transcriptional and epigenetic states, highlighting the role of distinct chromosomal backgrounds in cancer development.
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- Detailed analysis shows that genetic rearrangements of chromosome 3 drive certain myeloid leukemias by increasing EVI1 transcription through enhancer changes.
- A novel EVI1 RNA variant, created by mutations in the splicing factor SF3B1, contributes to acute myeloid leukemia transformation and is frequently found in these patients.
- Mutant SF3B1 promotes abnormal EVI1 splicing, enhancing stem cell self-renewal and accelerating leukemia development in mouse models, highlighting a crucial link between splicing mutations and myeloid leukemia pathogenesis.