HuH-7 reference genome profile: complex karyotype composed of massive loss of heterozygosity

Abstract

Human cell lines represent a valuable resource as in vitro experimental models. A hepatoma cell line, HuH-7 (JCRB0403), has been used extensively in various research fields and a number of studies using this line have been published continuously since it was established in 1982. However, an accurate genome profile, which can be served as a reliable reference, has not been available. In this study, we performed M-FISH, SNP microarray and amplicon sequencing to characterize the cell line. Single cell analysis of metaphases revealed a high level of heterogeneity with a mode of 60 chromosomes. Cytogenetic results demonstrated chromosome abnormalities involving every chromosome in addition to a massive loss of heterozygosity, which accounts for 55.3% of the genome, consistent with the homozygous variants seen in the sequence analysis. We provide empirical data that the HuH-7 cell line is composed of highly heterogeneous cell populations, suggesting that besides cell line authentication, the quality of cell lines needs to be taken into consideration in the future use of tumor cell lines.Electronic supplementary materialThe online version of this article (10.1007/s13577-018-0212-3) contains supplementary material, which is available to authorized users.

Identification of Characteristic Genomic Markers in Human Hepatoma Huh7 and Huh7.5.1-8 Cell Lines

“…POLD3 mutations have been identified repeatedly in cancer cells 31 , and they contribute to chromosomal instability 32 . We suspected that K70R mutations in POLD3 partly explain the large number of SNVs and indels and the frequent chromosome copy number changes in Huh7 33 .…”

Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2

“…This lineage was established in 1982 from a human hepatocellular carcinoma; it is therefore able to produce a great variety of substances secreted by the human liver ( 58 ) and has been used in the study of hepatitis C virus, SARS-CoV, and MERS-CoV ( 27 , 34 , 58 , 59 ). In the context of SARS-CoV-2, this cell line has been used in the study of infection mechanisms ( 23 , 39 ), the cytotoxicity of viruses from human hosts ( 22 , 60 ), and in pharmacological research ( 26 , 46 , 48 ).…”

Hepatic monoamine oxidase B is involved in endogenous geranylgeranoic acid synthesis in mammalian liver cells

“…As for the gene encoding MAOB, of note, there is an important difference between HuH-7 and Hep3B cell lines. The MAOB gene localizes to a short arm (Xp11.3) of X-chromosome and a Hep3B cell harbors a single intact X-chromosome (30,31), whereas in HuH-7 cells, many derivative chromosomes involving X-chromosome [der(X)t(X:14), +der(X)t(X;19), +der(4)t(X;4), der(11)t(X;11), der(13)t(X;13)] and the mosaic copy number observed at Xp are reported (32). These derivative chromosomes may make CRISPR/Cas9-HDR method difficult to knockout the MAOB gene in HuH-7 cells.…”