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Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies.
Cell Prolif
January 2025
MOE Key Laboratory of Bioinformatics, Beijing National Research Center for Information Science and Technology, Bioinformatics Division, Tsinghua University, Beijing, China.
Due to the similarity to human hepatocytes, porcine hepatocytes play an important role in hepatic research and drug evaluation. However, once hepatocytes were cultured in vitro, it was often prone to dedifferentiate, resulting in the loss of their characteristic features and normal functions, which impede their application in liver transplantation and hepatotoxic drugs evaluation. Up to now, this process has yet to be thoroughly investigated from the single-cell resolution and multi-omics perspective.
View Article and Find Full Text PDFRecipient sex and donor leukemic cell characteristics determine leukemogenesis in patient-derived models.
Haematologica
January 2025
University Clinic Tübingen, Department for Internal Medicine II, University of Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK), partner site Tübingen, a partnership between DKFZ and University Hospital Tübingen.
In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.
View Article and Find Full Text PDFHost hepatocyte senescence determines the success of hepatocyte transplantation in a mouse model of liver injury.
J Hepatol
January 2025
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh, EH16 4UU, United Kingdom. Electronic address:
Background & Aims: Hepatocyte transplantation has shown promise for genetic diseases of the hepatocytes but to date has shown limited efficacy for non-genetic forms of severe liver injury. Limited cell engraftment and poor function of donor hepatocytes in recipient livers impacts the clinical utility of hepatocyte cell therapy. The mechanisms underpinning this are poorly understood.
View Article and Find Full Text PDFInfluenza B virus infection alters the regenerative potential of murine alveolar type 2 pneumocytes.
mBio
December 2024
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
Unlabelled: Respiratory epithelial cells can survive direct infection by influenza viruses, and the long-term consequences of that infection have been characterized in a subset of proximal airway cell types. The impact on the cells that survive viral infection in the distal lung epithelia, however, is much less well-characterized. Utilizing a Cre-expressing influenza B virus (IBV) and a lox-stop-lox tdTomato reporter mouse model, we identified that alveolar type 2 (AT2) pneumocytes, a progenitor cell type in the distal lung, can survive viral infection.
View Article and Find Full Text PDFPartial microglial depletion and repopulation exert subtle but differential effects on amyloid pathology at different disease stages.
Sci Rep
December 2024
Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester, Rochester, NY, USA.
Article Synopsis
- CSF1R inhibitors can deplete and rejuvenate microglia in the brain, potentially improving conditions like Alzheimer's disease (AD).
- The study used 5xFAD mice to investigate how microglial depletion and repopulation affect amyloid plaque progression and found temporary improvements in plaque burden.
- Although the improvements weren't lasting, renewing microglia late in disease progression may enhance their responsiveness to noradrenergic signaling, suggesting a possible therapeutic approach for AD.
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