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Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs. We sequenced the genomes of two CTVT tumors and found that CTVT has acquired 1.9 million somatic substitution mutations and bears evidence of exposure to ultraviolet light. CTVT is remarkably stable and lacks subclonal heterogeneity despite thousands of rearrangements, copy-number changes, and retrotransposon insertions. More than 10,000 genes carry nonsynonymous variants, and 646 genes have been lost. CTVT first arose in a dog with low genomic heterozygosity that may have lived about 11,000 years ago. The cancer spawned by this individual dispersed across continents about 500 years ago. Our results provide a genetic identikit of an ancient dog and demonstrate the robustness of mammalian somatic cells to survive for millennia despite a massive mutation burden.
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http://dx.doi.org/10.1126/science.1247167 | DOI Listing |
Keio J Med
December 2024
Institute for the Advanced Study of Human Biology, Kyoto University Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University Center for iPS Cell Research and Application, Kyoto University.
The germ-cell lineage ensures the creation of new individuals, perpetuating/diversifying the genetic and epigenetic information across the generations. We have been investigating the mechanism for germ-cell development, and have shown that mouse embryonic stem cells (mESCs)/induced pluripotent stem cells (miPSCs) are induced into primordial germ cell-like cells (mPGCLCs) with a robust capacity both for spermatogenesis and oogenesis and for contributing to offspring. These works have served as a basis for elucidating key mechanisms during germ-cell development such as epigenetic reprogramming, sex determination, meiotic entry, and nucleome programming.
View Article and Find Full Text PDFDev Cell
December 2024
Department of Surgery, Henry Ford Health, Detroit, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, Lansing, MI, USA. Electronic address:
Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown.
View Article and Find Full Text PDFVirology
December 2024
VA San Diego Healthcare System, San Diego, CA, USA; Department of Medicine, University of California at San Diego, La Jolla, CA, USA. Electronic address:
Persistent HIV reservoir with different levels of proviral transcriptional activity represents a hurdle to HIV cure. The absence of a specific molecular signature or a "biomarker" to define cells latently infected with HIV limits reservoir eradication efforts. Biomarkers proposed in the literature define subsets of latently infected cells.
View Article and Find Full Text PDFCell Rep
December 2024
Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore; Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address:
Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2.
View Article and Find Full Text PDFCell Rep
December 2024
Center for Cell Lineage Technology and Engineering, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, China-New Zealand Belt and Road Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address:
Single-cell lineage tracing based on CRISPR-Cas9 gene editing enables the simultaneous linkage of cell states and lineage history at a high resolution. Despite its immense potential in resolving the cell fate determination and genealogy within an organism, existing implementations of this technology suffer from limitations in recording capabilities and considerable barcode dropout. Here, we introduce DuTracer, a versatile tool that utilizes two orthogonal gene editing systems to record cell lineage history at single-cell resolution in an inducible manner.
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