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Human cell transformation by combined lineage conversion and oncogene expression

Oncogene. 2021-07; 
Biswajyoti Sahu, Päivi Pihlajamaa, Kaiyang Zhang, Kimmo Palin, Saija Ahonen, Alejandra Cervera, Ari Ristimäki, Lauri A Aaltonen, Sampsa Hautaniemi, Jussi Taipale
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DNA Sequencing … Full-length coding sequences including stop codon for the TFs and oncogenes were obtained from GenScript (Piscataway, NJ) and cloned into the lentiviral expression vector pLenti6/V5-DEST using the Gateway recombination system (Thermo Fisher Scientific, Waltham, MA). … Get A Quote

摘要

Cancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination o... More

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