Transcriptomic data can help track Neandertal-derived RNA

Processes through which human-induced pluripotent stem cell (iPSC) lines are transformed into organoids have altered the way researchers explore developmental processes and allow them to decode the interaction between genes and tissue formation, particularly for organs where primary tissues are absent.

Image Credits: Billion Photos / Shutterstock.com
Image Credit: Billion Photos / Shutterstock.com

Scientists are now taking this technology and using it to explore the developmental impacts of Neandertal DNA.

Using iPSC lines to study the functions of archaic human DNA is an untapped but very interesting approach. No one has ever been able to look at the role Neandertal DNA plays during development.”

J. Gray Camp, Study Senior Author, Max Planck Institute for Evolutionary Anthropology

Camp also serves at the University of Basel in Switzerland.

Researchers have identified that around 2% of the genomes of modern humans from outside Africa contains Neandertal DNA. This ancient DNA is an outcome of mating that occurred between the two groups tens of thousands of years ago.

In the latest study, the researchers made use of resources from the Human Induced Pluripotent Stem Cells Initiative (HipSci)—an International Consortium that offers cell lines and data for research.

Almost all the cell lines and data in HipSci were taken from individuals of Northern European and UK descent. The scientists examined this cell line resource for its Neandertal DNA content and then annotated functional Neandertal variants for all the cell lines.

Some Neandertal alleles have relatively high frequency in this population. Because of that, this iPSC resource contains certain genes that are homozygous for Neandertal alleles, including genes associated with skin and hair color that are highly prevalent in Europeans.”

J. Gray Camp, Study Senior Author, Max Planck Institute for Evolutionary Anthropology

To produce brain organoids, Camp’s research team used four cell lines and produced single-cell RNA sequencing data to examine their cell composition. The researchers demonstrated that this transcriptomic data can perhaps be used for tracking Neandertal-derived RNA across the developmental processes.

This is a proof-of-principal study showing that you can use these resources to study the activity of Neandertal DNA in a developmental process. The real challenge will be scaling up the number of lines in one experiment, but this is already starting to be possible.”

J. Gray Camp, Study Senior Author, Max Planck Institute for Evolutionary Anthropology

Camp observed that this study could be extended to learn other archaic human populations, such as Denisovans, who have genes that are mainly present in Oceanian populations. Camp’s team is also planning to explore Neandertal alleles through HipSci and other resources.

Organoids can be used to study a number of different developmental processes and phenotypes controlled by Neandertal DNA, including the intestinal tract and digestion, cognition and neural function, and the immune response to pathogens,” Camp concluded.

Source:
Journal reference:

Dannemann, M., et al. (2020) Human Stem Cell Resources Are an Inroad to Neandertal DNA Functions. Stem Cell Reports. doi.org/10.1016/j.stemcr.2020.05.018.

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