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Neanderthal genes in a petri dish

Scientists are studying Neanderthal DNA in humans alive today using stem cells and organoids

Protocols for converting pluripotent stem cells (iPSCs) into organoids, mini-organs, allow researchers to study developmental processes in different organs and to unravel the connection between genes and tissue formation – especially in organs where primary tissue is not available. Researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig and the University of Basel use this technology to study the effects of Neanderthal DNA in modern humans.

"Using iPSC lines to study the functions of archaic DNA in contemporary humans is a largely unexplored but very interesting approach," says senior author J. Gray Camp from the Max Planck Institute for Evolutionary Anthropology in Leipzig and the University of Basel in Switzerland. "Nobody has been able to study the role of Neanderthal DNA during development."

About two percent of the genomes of modern humans living outside of Africa are made up of Neanderthal DNA. This archaic DNA is a result of the mixing of both groups tens of thousands of years ago.

In the new study, the team used resources from the Human Induced Pluripotent Stem Cells Initiative (HipSci), an international consortium providing data and cell lines for research. Almost all of the data and cell lines in HipSci are from people of British and Northern European descent. The researchers analyzed these cell lines for their Neanderthal DNA content and annotated functional Neanderthal variants for each of the cell lines.

"Some Neanderthal alleles are relatively common in this population," Camp explains. "Therefore, this iPSC resource contains certain genes homozygous for Neanderthal alleles, including genes associated with skin and hair color, which are very common in Europeans."

Camp's team converted four cell lines into cerebral organoids, mini versions of human brains in their early stages of development, and sequenced individual cells from these organoids to study their composition. They showed that the transcriptomic data could be used to trace Neanderthal-derived RNA across developmental processes. "This study provides evidence that these resources can be used to study the activity of Neanderthal DNA in a developmental process," says Camp. "The real challenge will be to increase the number of lines per experiment, but that is already becoming possible."

Camp notes that this research could be extended to study other ancient human populations, including the Denisovans, whose genes are found primarily in oceanic populations today. His team also plans to continue studying Neanderthal alleles using HipSci and other resources. "Organoids can be used to study a number of different developmental processes and phenotypes controlled by Neanderthal DNA, including gut and digestion, cognition and neuronal function, and the immune response to pathogens," says Camp.

Im Neandertal Stem Cell Resource Browser researchers make their data available to the scientific community for future research.

Source: Press release from the Max Planck Institute for Evolutionary Anthropology from June 18.06.2020th, XNUMX




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