WFRF:(Ristimaki A)
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 02447naa a2200373 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:147221562 | |
| 003 | SwePub | |
| 008 | 240701s2021 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1472215622 URI |
| 024 | 7 | a https://doi.org/10.1038/s41388-021-01940-02 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Sahu, B4 aut |
| 245 | 1 0 | a Human cell transformation by combined lineage conversion and oncogene expression |
| 264 | c 2021-07-23 | |
| 264 | 1 | b Springer Science and Business Media LLC,c 2021 |
| 520 | a 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 of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis. | |
| 700 | 1 | a Pihlajamaa, P4 aut |
| 700 | 1 | a Zhang, KY4 aut |
| 700 | 1 | a Palin, K4 aut |
| 700 | 1 | a Ahonen, S4 aut |
| 700 | 1 | a Cervera, A4 aut |
| 700 | 1 | a Ristimaki, A4 aut |
| 700 | 1 | a Aaltonen, LA4 aut |
| 700 | 1 | a Hautaniemi, S4 aut |
| 700 | 1 | a Taipale, Ju Karolinska Institutet4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Oncogened : Springer Science and Business Media LLCg 40:36, s. 5533-5547q 40:36<5533-5547x 1476-5594x 0950-9232 |
| 856 | 4 | u https://www.nature.com/articles/s41388-021-01940-0.pdf |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:147221562 |
| 856 | 4 8 | u https://doi.org/10.1038/s41388-021-01940-0 |
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