Cell reports · 2023
Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing.
СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод пока не подготовлен
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Craig Amanda J, Silveira Maruhen A Datsch, Ma Lichun, Revsine Mahler, Wang Limin, Heinrich Sophia, Rae Zachary, Ruchinskas Allison, Dadkhah Kimia, Do Whitney, Behrens Shay, Mehrabadi Farid R, Dominguez Dana A, Forgues Marshonna, Budhu Anuradha, Chaisaingmongkol Jittiporn, Hernandez Jonathan M, Davis Jeremy L, Tran Bao, Marquardt Jens U, Ruchirawat Mathuros, Kelly Michael, Greten Tim F, Wang Xin W
Аннотация
Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.