HeLa-CCL2 cell heterogeneity studied by single-cell DNA and RNA sequencing.

Wan-Er Hu,Xiao-Dong Su,Shi-Cheng Wei,Xin Zhang,Jing-Wei Yang,Yuan Yang,Qiu-Fang Guo,Debarka Sengupta

doi:10.1371/journal.pone.0225466

Abstract

The HeLa cells are the earliest and mostly used laboratory human cells for biomedical particularly cancer research. They were derived from a patient’s cervical cancerous tissue, and are known for their heterogeneous cellular origin and variable genomic landscapes. Single-cell sequencing techniques with faithful linear and uniformly amplified genomes (DNA) and transcriptomes (RNA) may facilitate the study of cellular differences at the individual cell level. In this work, we have performed single-cell DNA and RNA sequencing with HeLa-CCL2 cells to study their heterogeneity. We have studied the complexity of copy number variations (CNVs) of HeLa-CCL2 genome at the single cell level, and revealed the transcriptomic heterogeneity of HeLa-CCL2. We also analyzed the relationship between genome and transcriptome at the single-cell level, and found overall correlation between CNV and transcriptome expression patterns. Finally, we concluded that although single-cell sequencing techniques are applicable to study heterogeneous cells such as HeLa-CCL2, the data analyses need to be more careful and well controlled.

Highlights

In 1951, Gey et al isolated the cancer tissue from Henrietta Lacks, a woman with cervical cancer, and established the HeLa cell line in vitro, which was the first human-derived immortalized cell line [1]
We have studied the complexity of copy number variations (CNVs) of HeLa-CCL2 genome at the single cell level, and revealed the transcriptomic heterogeneity of HeLa-CCL2
3.2 Single-cell DNA sequencing results depicted the heterogeneous characters of HeLa-CCL2 CNVs with low resolution

Summary

Introduction

In 1951, Gey et al isolated the cancer tissue from Henrietta Lacks, a woman with cervical cancer, and established the HeLa cell line in vitro, which was the first human-derived immortalized cell line [1]. In the sixty plus years, HeLa became the most wildly used cell line in biomedical research, and produced results for more than 70,000 publications (searched from PubMed). The HeLa cells had undergone multiple generations of propagations. HeLa cells have derived more than 300 progeny strains utilized in many fields of life sciences. HeLa-S3 can grow as suspension cultures, and is widely used in the field of cytology. The morphology of HeLa-Kyoto is more favorable for imaging, and there are massive progeny cell lines derived from it that are transfected with different fluorescent proteins.

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