‘Mini brains’ grown from human stem cells with Neanderthal DNA

Scientists have grown ‘mini brains’ from human stem cells containing Neanderthal DNA to help shed light on how it has impacted our development.

Researchers from Germany showed how genetic material derived from our distant Neanderthal cousins can be identified and tracked in the model organs as they grow.

Past studies have shown that around 2 percent of the gene pool of modern humans outside of Africa is composed of Neanderthal DNA.

This genetic heritage was acquired as a result of various episodes of interbreeding between our ancestors and Neanderthals tens of thousands of years ago. 

In their study, geneticist Gray Camp of the Max Planck Institute for Evolutionary Anthropology in Germany and colleagues analysed cell lines taken from the Human Induced Pluripotent Stem Cells Initiative — or ‘HipSci’, as it is dubbed.

This international resource was established to provide data and cell lines for genetic studies — and nearly all of the latter are derived from individuals of UK and northern European descent, meaning that they contain traces of Neanderthal DNA.

‘Some Neanderthal alleles have [a] relatively high frequency in this population,’ Dr Camp explained. An allele is a variant form of a given gene.

‘Because of that, this induced pluripotent stem cell resource contains certain genes that are homozygous for Neanderthal alleles, including genes associated with skin and hair colour that are highly prevalent in Europeans.’

A homozygous gene is one where both alleles — one inherited from each parent — are the same, meaning that they will be expressed even if they are not dominant.

The researchers set about identifying these traces of genetic material from our ancient relatives — which were acquired as a product of cross-species interbreeding — and predicting which functioning variations of such might also have existed.

They then went on to use five of the cell lines to create so-called ‘organoids’ that resemble brain matter — and studied their cell composition using RNA sequencing.

Finally, the team were able to demonstrate that the data this provided allowed them to track Neanderthal-derived RNA across various development processes.

‘Using induced pluripotent stem cells lines to study the functions of archaic human DNA is an untapped but very interesting approach,’ said Dr Camp. 

‘No one has ever been able to look at the role Neanderthal DNA plays during development,’ he said, noting that the present proof-of-principal study had overcome this hurdle — but that there is more work to be done.

‘The real challenge will be scaling up the number of lines in one experiment, but this is already starting to be possible,’ he added. 

With their initial study complete, the researchers are now looking to further investigate Neanderthal DNA, including how it impacts other areas of the body. ‘Organoids can be used to study a number of different developmental processes and phenotypes controlled by Neanderthal DNA,’ said Dr Camp. These, he added, include the ‘intestinal tract and digestion, cognition and neural function, and the immune response to pathogens’

With their initial study complete, the researchers are now looking to further investigate Neanderthal DNA, including how it impacts other areas of the body.

‘Organoids can be used to study a number of different developmental processes and phenotypes controlled by Neanderthal DNA,’ said Dr Camp. 

These, he added, include the ‘intestinal tract and digestion, cognition and neural function, and the immune response to pathogens’.

In addition, Dr Camp explained, the principle behind the research might be similarly employed top investigate other ancient human populations — such as, for example, the Denisovans, whose genes can primarily be found in populations in Oceania. 

The full findings of the study were published in the journal Stem Cell Reports.

A close relative of modern humans, Neanderthals went extinct 40,000 years ago

The Neanderthals were a close human ancestor that mysteriously died out around 40,000 years ago.

The species lived in Africa with early humans for millennia before moving across to Europe around 300,000 years ago.

They were later joined by humans, who entered Eurasia around 48,000 ears ago.  

The Neanderthals were a cousin species of humans but not a direct ancestor – the two species split from a common ancestor –  that perished around 50,000 years ago. Pictured is a Neanderthal museum exhibit

These were the original ‘cavemen’, historically thought to be dim-witted and brutish compared to modern humans.

In recent years though, and especially over the last decade, it has become increasingly apparent we’ve been selling Neanderthals short.

A growing body of evidence points to a more sophisticated and multi-talented kind of ‘caveman’ than anyone thought possible.

It now seems likely that Neanderthals had told, buried their dead, painted and even interbred with humans.   

They used body art such as pigments and beads, and they were the very first artists, with Neanderthal cave art (and symbolism) in Spain apparently predating the earliest modern human art by some 20,000 years.

They are thought to have hunted on land and done some fishing. However, they went extinct around 40,000 years ago following the success of Homo sapiens in Europe.