Male and female stem cells derived from same person

Genetically near-identical male and female induced pluripotent stem cells (iPSCs) have been derived from the same person for the first time.

Biological sex is typically determined by the presence of either two X chromosomes (XX) in females, or one X and one Y chromosome (XY) in males. Researchers in Israel derived the stem cells from a donor with Kleinfelter syndrome, who has two X and one Y chromosomes (XXY). Aside from the difference in sex chromosomes, the two cell lines have the same DNA, creating a unique model for the study of sex differences in disease and therapeutics.

'For the first time, we now have cells that are absolutely identical genetically, but in both male and female versions,' said lead author Professor Benjamin Reubinoff from Hadassah University Medical Centre, Jerusalem. 'This means that we can compare and contrast how they respond to the medication, or use them to model illness, without any of the "noise" we're used to.'

Men and women experience different disease incidence rates and symptoms as well as different responses to medication, due to a wide variety of factors including genetics, hormones, and lifestyle, making it difficult to study differences that arise solely from gender. As a result, since 2016 the US National Institutes of Health requires sex as a biological variable to be considered in all research it funds.

The iPSCs were generated from blood stem cells, not a new technique in itself. However, blood stem cells can accumulate mutations over time, leading to separate populations of cells with slightly different genomes (see BioNews 1146).

'The blood cell donor to our study was unique and one of the few Klinefelter sufferers in the world whose blood also had small subpopulations of normal male (XY) and female (XX) cells,' said first author Dr Ithai Waldhorn.

Publishing their results in Stem Cell Reports, the researchers have already detected differences between the male and female iPSCs, with female cells more closely resembling an earlier pluripotent state than the male cells. They demonstrated the ability of brain cells to be generated from both groups of iPSCs, and noted differences in gene expression between them, with male brain cells showing higher expression levels of genes linked to schizophrenia and cerebral palsy, diseases which have higher prevalence in males.

'The unique stem cell system we have developed will lead to new discoveries about gender differences, and can help compare the efficacy and toxicity of drugs,' said Professor Reubinoff.