Studying the Neanderthal DNA found in modern humans using stem cells and organoids

Date:
June 18, 2020
Source:
Cell Press
Summary:
Protocols that allow the transformation of human induced
pluripotent stem cell (iPSC) lines into organoids have changed
the way scientists can study developmental processes and enable
them to decipher the interplay between genes and tissue formation,
particularly for organs where primary tissue is not available. Now,
investigators are taking this technology and applying it to study
the developmental effects of Neanderthal DNA.



FULL STORY ========================================================================== Protocols that allow the transformation of human induced pluripotent
stem cell (iPSC) lines into organoids have changed the way scientists can
study developmental processes and enable them to decipher the interplay
between genes and tissue formation, particularly for organs where primary tissue is not available. Now, investigators are taking this technology
and applying it to study the developmental effects of Neanderthal DNA. The findings are reported June 18 in the journal Stem Cell Reports.


========================================================================== "Using iPSC lines to study the functions of archaic human DNA is an
untapped but very interesting approach," says senior author J. Gray Camp
of the Max Planck Institute for Evolutionary Anthropology in Germany
and the University of Basel in Switzerland. "No one has ever been
able to look at the role Neanderthal DNA plays during development."
Studies have found that about 2% of the genomes of modern humans from
outside Africa are composed of Neanderthal DNA. This archaic DNA is a
result of mating between the two 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
that provides data and cell lines for research. Nearly all of the data
and cell lines in HipSci are from people of UK and Northern European
descent. The researchers analyzed this cell line resource for its
Neanderthal DNA content and annotated functional Neanderthal variants
for each of the cell lines.

"Some Neanderthal alleles have relatively high frequency in this
population," Camp explains. "Because of that, this iPSC resource contains certain genes that are homozygous for Neanderthal alleles, including
genes associated with skin and hair color that are highly prevalent in Europeans." Camp's team used five cell lines to generate brain organoids
and generated single-cell RNA sequencing data to analyze their cell composition. They showed that this transcriptomic data could be used to
track Neanderthal-derived RNA across developmental processes. "This is
a proof-of-principal study showing that you can use these resources to
study the activity of Neanderthal DNA in a developmental process," Camp
says. "The real challenge will be scaling up the number of lines in one experiment, but this is already starting to be possible." Camp notes that
this research could be expanded to study other ancient human populations, including Denisovans, which have genes that are present primarily in
Oceanian populations. 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 the intestinal tract and digestion, cognition
and neural function, and the immune response to pathogens," he concludes.

The researchers have generated a web browser with this information to
make the data easily accessible for future research.


========================================================================== Story Source: Materials provided by Cell_Press. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Michael Dannemann, Zhisong He, Christian Heide, Benjamin Vernot,
Leila
Sidow, Sabina Kanton, Anne Weigert, Barbara Treutlein, Svante
Pa"a"bo, Janet Kelso, J. Gray Camp. Human Stem Cell Resources Are
an Inroad to Neandertal DNA Functions. Stem Cell Reports, 2020;
DOI: 10.1016/ j.stemcr.2020.05.018 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200618150306.htm

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