Comparison of induced neurons reveals slower structural and functional maturation in humans than in apes

Maria Schörnig,Sebastian Ebert,Barbara Treutlein,Anne Weigert,Wulf Hevers,Xiangchun Ju,Nael Nadif Kasri,Theresa Schaffer,Luise Fast,Benjamin Marco Peter,Elena Taverna,Sabina Kanton

doi:10.7554/elife.59323

Abstract

We generated induced excitatory neurons (iNeurons, iNs) from chimpanzee, bonobo, and human stem cells by expressing the transcription factor neurogenin-2 (NGN2). Single-cell RNA sequencing showed that genes involved in dendrite and synapse development are expressed earlier during iNs maturation in the chimpanzee and bonobo than the human cells. In accordance, during the first 2 weeks of differentiation, chimpanzee and bonobo iNs showed repetitive action potentials and more spontaneous excitatory activity than human iNs, and extended neurites of higher total length. However, the axons of human iNs were slightly longer at 5 weeks of differentiation. The timing of the establishment of neuronal polarity did not differ between the species. Chimpanzee, bonobo, and human neurites eventually reached the same level of structural complexity. Thus, human iNs develop slower than chimpanzee and bonobo iNs, and this difference in timing likely depends on functions downstream of NGN2.

Highlights

Differences in cognitive abilities between humans and non-human primates are thought to depend on greater numbers of neurons and more complex neural architectures in humans (Geschwind andRakic, 2013; Herculano-Houzel, 2012; Smaers et al, 2017)
All eight cell lines were used for electrophysiological recordings
Differentiation was characterized by a downregulation of the stem cell markers NANOG, OCT4, and SOX2 in both ape and human cells (Figure 3—figure supplement 1C), by a change in cellular morphology and by the extension of neurites (Figure 1C)

Summary

Introduction

Differences in cognitive abilities between humans and non-human primates are thought to depend on greater numbers of neurons and more complex neural architectures in humans (Geschwind andRakic, 2013; Herculano-Houzel, 2012; Smaers et al, 2017). Differences in cognitive abilities between humans and non-human primates are thought to depend on greater numbers of neurons and more complex neural architectures in humans Primate brains contain a greater number of neural stem and progenitor cells that generate neurons (Florio and Huttner, 2014; Borrell and Reillo, 2012; Lui et al, 2011; Smart et al, 2002). Given the role of pyramidal neurons in higher cognitive functions (Goldman-Rakic, 1999), a higher degree of connectivity in human neocortex than in other primates could provide a basis for human-specific cognitive abilities (DeFelipe, 2011; Bianchi et al, 2013a; Bianchi et al, 2013b; Elston et al, 2001)

Methods

Results

Conclusion