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1. Cells of the adult human heart

   https://doi.org/10.1038/s41586-020-2797-4  

   Litviňuková, Monika; Talavera-López, Carlos; Maatz, Henrike; Reichart, Daniel; Worth, Catherine L.; Lindberg, Eric L.; Kanda, Masatoshi; Polanski, Krzysztof; Heinig, Matthias; Lee, Michael; et al (December 2020, Nature)

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   Abstract Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies. 

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2. Two distinct trophectoderm lineage stem cells from human pluripotent stem cells

   https://doi.org/10.1016/j.jbc.2021.100386  

   Mischler, Adam; Karakis, Victoria; Mahinthakumar, Jessica; Carberry, Celeste K.; San Miguel, Adriana; Rager, Julia E.; Fry, Rebecca C.; Rao, Balaji M. (January 2021, Journal of Biological Chemistry)

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3. Genetic physical unclonable functions in human cells

   https://doi.org/10.1126/sciadv.abm4106  

   Li, Yi; Bidmeshki, Mohammad Mahdi; Kang, Taek; Nowak, Chance M.; Makris, Yiorgos; Bleris, Leonidas (May 2022, Science Advances)

   CRISPR-engineered physical unclonable functions establish a foundational security technology for provenance attestation protocols. 

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4. Mechanical fatigue of human red blood cells

   https://doi.org/10.1073/pnas.1910336116  

   Qiang, Yuhao; Liu, Jia; Dao, Ming; Suresh, Subra; Du, E. (October 2019, Proceedings of the National Academy of Sciences)

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   Fatigue arising from cyclic straining is a key factor in the degradation of properties of engineered materials and structures. Fatigue can also induce damage and fracture in natural biomaterials, such as bone, and in synthetic biomaterials used in implant devices. However, the mechanisms by which mechanical fatigue leads to deterioration of physical properties and contributes to the onset and progression of pathological states in biological cells have hitherto not been systematically explored. Here we present a general method that employs amplitude-modulated electrodeformation and microfluidics for characterizing mechanical fatigue in single biological cells. This method is capable of subjecting cells to static loads for prolonged periods of time or to large numbers of controlled mechanical fatigue cycles. We apply the method to measure the systematic changes in morphological and biomechanical characteristics of healthy human red blood cells (RBCs) and their membrane mechanical properties. Under constant amplitude cyclic tensile deformation, RBCs progressively lose their ability to stretch with increasing fatigue cycles. Our results further indicate that loss of deformability of RBCs during cyclic deformation is much faster than that under static deformation at the same maximum load over the same accumulated loading time. Such fatigue-induced deformability loss is more pronounced at higher amplitudes of cyclic deformation. These results uniquely establish the important role of mechanical fatigue in influencing physical properties of biological cells. They further provide insights into the accumulated membrane damage during blood circulation, paving the way for further investigations of the eventual failure of RBCs causing hemolysis in various hemolytic pathologies. 

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5. The fidelity of transcription in human cells

   https://doi.org/10.1073/pnas.2210038120  

   Chung, Claire; Verheijen, Bert M.; Zhang, Xinmin; Huang, Biao; Coakley, Aeowynn; McGann, Eric; Wade, Emily; Dinep-Schneider, Olivia; LaGosh, Jessica; Anagnostou, Maria-Eleni; et al (January 2023, Proceedings of the National Academy of Sciences)

   To determine the error rate of transcription in human cells, we analyzed the transcriptome of H1 human embryonic stem cells with a circle-sequencing approach that allows for high-fidelity sequencing of the transcriptome. These experiments identified approximately 100,000 errors distributed over every major RNA species in human cells. Our results indicate that different RNA species display different error rates, suggesting that human cells prioritize the fidelity of some RNAs over others. Cross-referencing the errors that we detected with various genetic and epigenetic features of the human genome revealed that the in vivo error rate in human cells changes along the length of a transcript and is further modified by genetic context, repetitive elements, epigenetic markers, and the speed of transcription. Our experiments further suggest that BRCA1, a DNA repair protein implicated in breast cancer, has a previously unknown role in the suppression of transcription errors. Finally, we analyzed the distribution of transcription errors in multiple tissues of a new mouse model and found that they occur preferentially in neurons, compared to other cell types. These observations lend additional weight to the idea that transcription errors play a key role in the progression of various neurological disorders, including Alzheimer’s disease. 

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