A way to stabilize haploidy in animal cells

August 15, 2017, Centro Nacional de Investigaciones Oncológicas
SKY analysis of haploid and diploid cells. Credit: CNIO

The emergence in recent years of the first mammalian haploid cell lines has raised great expectations in the scientific community. Despite their potential, these cultures present some issues that complicate their use because haploidy is unstable and can be lost quickly. The Genomic Instability Group at the Spanish National Cancer Research Centre (CNIO) has offered an explanation of this phenomenon and proposes a way to overcome it. This work has been published in the journal Proceedings of the National Academy of Sciences (PNAS).

With the exception of the sperm or ovules, cells contain two sets of , one from each parent. However, organisms with a single set of chromosomes (haploids), such as yeast, are extremely useful for genetic studies and are crucial in identifying key genes and pathways. Laboratory yeasts enabled studies on autophagy by Yoshinori Ohsumi, which earned him the Nobel Prize in Medicine in 2016, and the Nobel-winning discovery of the cell cycle regulatory genes.

"As [yeast] has only one set of chromosomes, it is very easy to find interesting mutants, as all you have to do is to alter a single allele to produce a phenotype," says Oscar Fernández-Capetillo, head of the Genomic Instability Group and the leader of the research project. "In mammals, in the absence of haploid cells, other approaches have been used to identify key genes, such as interfering RNA, but they are sub-optimal methods. All this changed five years ago when haploid cells were discovered in a leukaemia patient (KBM7 and HAP1) and with the emergence of techniques to create mammalian haploid embryonic stem cells, developed originally by Anton Wutz," continues Fernández-Capetillo.

However, the cultures of such mammalian haploid cells become diploid within a few days. This phenomenon, which has been called "diploidization," is what Fernández-Capetillo's group has been studying. Their findings suggest that the loss of haploid cells is due to their limited viability, and therefore, they are replaced by existing diploid cells in the cultures.

"When you try to isolate haploid cells, it is very difficult to take only one; you usually separate several so you always drag along a diploid. When you culture them, you invariably observe that the haploid cells die and the diploid cells become the majority," he says. "We now know that this happens because the haploid cells activate death mechanisms via p53."

Their studies show that the problem arises when the haploid cells try to separate their chromosomes during mitosis. The machinery involved in cell division has been designed to handle a fixed amount of DNA (46 chromosomes). When there is more (polyploidy) or less (haploidy), mitosis is more prone to errors during the segregation of the chromosomes, and this activates p53. This is the reason why haploid cell cultures do not thrive. By eliminating p53, as this study demonstrates, haploid cells are able to survive.

"Our findings should facilitate the use of animal haploid , making them accessible to a broader range of laboratories and technologies," the authors conclude. Currently, the group is trying to discover chemical forms of stabilizing haploidy in and is exploring strategies that would allow the creation of organs or even animals that only have a maternal set of chromosomes.

Explore further: First 'haploid' human stem cells could change the face of medical research

More information: A p53-dependent response limits the viability of mammalian haploid cells Proceedings of the National Academy of Sciences (2017). www.pnas.org/cgi/doi/10.1073/pnas.1705133114

Related Stories

Fungal biology: Finding yeast's better half

July 31, 2013

Scientists long believed that the fungal pathogen Candida albicans was incapable of producing haploid cells—which contain only one copy of each chromosome, analagous to eggs and sperm—for mating. Mixing of genes in sexual ...

Rewiring stem cells

January 9, 2014

A fast and comprehensive method for determining the function of genes could greatly improve our understanding of a wide range of diseases and conditions, such as heart disease, liver disease and cancer.

The genetics behind being Not Like Daddy

February 22, 2017

A common strategy to create high-yielding plants is hybrid breeding - crossing two different inbred lines to obtain characteristics superior to each parent. However, getting the inbred lines in the first place can be a hassle. ...

Yeast's lifestyle couples mating with meiosis

January 5, 2014

From a biological point of view, the world's most exotic sex lives may be the ones lived by fungi. As a kingdom, they are full of surprises, and a new one reported in the journal Nature seems sure to titillate the intellects ...

Recommended for you

Engineering cellular function without living cells

March 25, 2019

Genes in living cells are activated – or not – by proteins called transcription factors. The mechanisms by which these proteins activate certain genes and deactivate others play a fundamental role in many biological processes. ...

What ionized the universe?

March 25, 2019

The sparsely distributed hot gas that exists in the space between galaxies, the intergalactic medium, is ionized. The question is, how? Astronomers know that once the early universe expanded and cooled enough, hydrogen (its ...

Catalyst advance removes pollutants at low temperatures

March 25, 2019

Researchers at Washington State University, University of New Mexico, Eindhoven University of Technology, and Pacific Northwest National Laboratory have developed a catalyst that can both withstand high temperatures and convert ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.