The research world’s most famous human cell has had its genome decoded, and it’s a mess. German researchers this week report the genome sequence of the HeLa cell line, which originates from a deadly cervical tumor taken from a patient named Henrietta Lacks.

Established after Lacks died in 1951, HeLa cells were the first human cells to grow well in the laboratory. The cells have contributed to more than 60,000 research papers, the development of a polio vaccine in the 1950s and, most recently, an international effort to characterize the genome, known as ENCODE.

Previous work showed that HeLa cells, like many tumors, have bizarre, error-filled genomes, with one or more extra copies of many chromosomes. To get a closer look at these alterations, a team led by Lars Steinmetz, a geneticist at the European Molecular Biology Laboratory in Heidelberg, Germany, sequenced the popular 'Kyoto' version of the cell line and compared the sequence with that of a reference human genome. The team's results are published in G3.

Steinmetz’s team confirmed that HeLa cells contain one extra version of most chromosomes, with up to five copies of some. Many genes were duplicated even more extensively, with four, five or six copies sometimes present, instead of the usual two.  Furthermore, large segments of chromosome 11 and several other chromosomes were reshuffled like a deck of cards, drastically altering the arrangement of the genes.

Without the genome sequence of Lacks’ healthy cells or that of her original tumor, it is difficult to trace the origin of these alterations. Steinmetz points out that other cervical tumors have massive rearrangements on chromosome 11, so the changes in the HeLa cell may have contributed to Lacks’ tumor.

Potential uses
Having been replicating in labs around the world for six decades, HeLa cells have also accrued errors not present in the original tumor DNA. Moreover, not all HeLa cells are identical, and Steinmetz says that it would be interesting to chart the cell’s evolution.

Whatever their origin, the genetic changes raise questions over the widespread use of HeLa cells as models for human cell biology, Steinmetz says. For instance, his team found that around 2000 genes are expressed at levels higher than those of normal human tissues because of the duplications. Alternative cell lines, such as induced pluripotent stem cells generated from patient skin cells, offer a more accurate window on human biology, he says.

Mathew Garnett, a cancer biologist at the Wellcome Trust Sanger Institute near Cambridge, UK, says that HeLa cells could prove useful for studying aspects of the biology of cervical tumors, such as their response to cancer drugs. In recent years, the genomes of many cervical tumors have been sequenced, and so it should be possible to see how these compare with the HeLa genome.

Steinmetz also points out that thousands of research papers based on HeLa cells, along with HeLa resources such as genetically manipulated lines and now a genome, means that labs will continue to stock the cells, even if they are not a perfect model of human biology. “These are not going to go out of fashion over the next 10 years,” he says. "I’m not sure where we’re going to be 20 years from now."

This article is reproduced with permission from the magazine Nature. The article was first published on March 15, 2013.

5 Comments

1. 1. janine robidoux 06:41 PM 3/15/13

   It is a pity that her cancer cells were used without the family's permission. I know that there is a book about her life and I hope that her family has been compensated for using her cells without their consent.

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2. 2. jshieldsjr in reply to janine robidoux 08:37 PM 3/15/13

   Indeed, the book is "The Immortal Henrietta Lacks." It is a remarkable story, not only about Henrietta Lacks and her family, but about the author's quest to make her story public and the difficulties gaining acceptance from the family, who had endured years of futility in their quest to share in the income stream from her cells that had been taken with neither her permission nor her knowledge. It is a heart-wrenching story, full of ironies both large and small. It does not end happily.

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3. 3. ErnestPayne 02:41 PM 3/16/13

   Jshields. I just read that book a couple of months ago. Absolutely fascinating and one of the best books I have ever read in 60+ years. This is just another chapter in the life of the cells.

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4. 4. alma vasquez 10:27 AM 3/20/13

   It is those "errors" that kept the line of cells alive. It would be interesting to see which genetic "error" enabled the cells to live so long outside a human host.

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5. 5. JonathanEisen 10:08 AM 3/21/13

   I find it very disturbing that this paper / work was done without getting informed consent from the family. This genome contains significant amounts of information that relate to their genomes too. One would not be allowed to take DNA from a person without their permission and sequence the genome and post it. Why should that be OK here? I get that people have worked on HeLa cells for many years but this is a step beyond normal experimental studies and shame on the authors for not involving the family in a decision to do this.

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