Abstract
The cellular, molecular and functional comparison of neurons from closely related species is crucial in evolutionary neurobiology. The access to living tissue and post-mortem brains of humans and non-human primates is limited and the state of the tissue might not allow recapitulating important species-specific differences. A valid alternative is offered by neurons derived from induced pluripotent stem cells (iPSCs) obtained from humans and non-human apes and primates. We will review herein the contribution of iPSCs-derived neuronal models to the field of evolutionary neurobiology, focusing on species-specific aspects of neuron’s cell biology and timing of maturation. In addition, we will discuss the use of iPSCs for the study of ancient human traits.
Highlights
DISCOVERY AND USE OF induced pluripotent stem cells (iPSCs)The closest living relatives of modern humans are the great apes and among them, chimpanzees and bonobos who’s lineages split from the last common ancestor with humans about 5-10 million years ago (Pääbo, 2014)
The cellular, molecular and functional comparison of neurons from closely related species is crucial in evolutionary neurobiology
A valid alternative is offered by neurons derived from induced pluripotent stem cells obtained from humans and non-human apes and primates
Summary
The closest living relatives of modern humans are the great apes and among them, chimpanzees and bonobos who’s lineages split from the last common ancestor with humans about 5-10 million years ago (Pääbo, 2014). Similar to embryonic stem cells (ESCs), iPSCs can differentiate into many different cell types, for example neurons (Reubinoff et al, 2001; Zhang et al, 2001), insulin-producing beta cells (Assady et al, 2001), cardiovascular cells (He et al, 2003), hematopoietic cells (Kaufman et al, 2001; Chadwick et al, 2003), and many other cells of the human body (Williams et al, 2012), or self-organize into complex three-dimensional structures containing multiple cell types that resemble human tissues, called organoids (Lancaster and Knoblich, 2014; Clevers, 2016) These stem cell-derived systems can be used to study disease-associated pathomechanisms in vitro, test drugs, develop tissue replacement and patient specific therapies and to explore how natural variation between humans and non-human primates impact development, cell biology and disease. Through these examples we will illustrate how iPSCs have been successfully used to: (1) model brain evolution, (2) study human-ape differences in neuronal structure and function and (3) gain insight into brain development of human extinct relatives, such as Neanderthals and Denisovans using CRISPR/Cas genetic engineering
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