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

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 t...

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Bibliographic Details
Published in:eLife 2021-01, Vol.10
Main Authors: Schörnig, Maria, Ju, Xiangchun, Fast, Luise, Ebert, Sebastian, Weigert, Anne, Kanton, Sabina, Schaffer, Theresa, Nadif Kasri, Nael, Treutlein, Barbara, Peter, Benjamin Marco, Hevers, Wulf, Taverna, Elena
Format: Article
Language:English
Subjects:
Analysis
Animals
Antibodies
Axons
bonobo
Brain
Cell cycle
Cell Differentiation
Chimpanzee
Cognitive ability
Developmental Biology
evolution
Humans
Maturation
Monkeys & apes
Morphology
Neurites - metabolism
neurodevelopment
Neurogenesis
Neurogenins
neuronal function
neuronal maturation
Neurons
Neurons - physiology
Neuroscience
Pan paniscus - physiology
Pan troglodytes - physiology
Polarity
RNA sequencing
Species Specificity
Stem cells
Structure-function relationships
Synapses
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.59323