Journal Article

Differences and similarities between human and chimpanzee neural progenitors during cerebral cortex development

Kanton, Sabina, Lachmann, Robert, Badsha, Farhath, Okita, Keisuke, He, Zhisong, Treutlein, Barbara, Köhler, Kathrin, Voigt, Birger, Vernot, Benjamin, Camp, J Gray, Maricic, Tomislav, Huttner, Wieland B, Pääbo, Svante, Mora-Bermúdez, Felipe

2016

Overview

Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistofluorescence, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution. The human brain is about three times as big as the brain of our closest living relative, the chimpanzee. Moreover, a part of the brain called the cerebral cortex – which plays a key role in memory, attention, awareness and thought – contains twice as many cells in humans as the same region in chimpanzees. Networks of brain cells in the cerebral cortex also behave differently in the two species. How these species differences arise is not clear, but it likely occurs in the earliest phases of development when brain stem and progenitor cells divide and give rise to cerebral cortex cells in the growing brain. To study the earliest stages of brain development, researchers often use human brain cells grown in the laboratory. Under the right conditions, cells collected from adult humans and other animals can be reprogrammed to behave like brain stem cells. Recently, researchers have been able to use these reprogrammed cells to make tissue that resembles the brain in petri dishes, known as brain organoids. Mora-Bermúdez, Badsha, Kanton, Camp et al. have now analysed brain organoids grown from reprogrammed human, chimpanzee and orangutan cells. The experiments showed that the human and chimpanzee brain organoids were remarkably similar in many ways including in the mix of cell types and in how these cells were arranged. Mora-Bermúdez et al. then used live microscopy to show that progenitor cells that form the human cerebral cortex spend around 50% more time in a stage of the cell division process called metaphase compared to the same cells from chimpanzees or orangutans. Metaphase is the part of the division process when the cell makes sure that structures called chromosomes, which carry the cell’s DNA, can be separated and distributed equally between the two daughter cells. Mora-Bermúdez et al. also found that progenitor cells more likely to become neurons sooner had a shorter metaphase than progenitor cells more likely to remain proliferating as stem cells for longer. This suggests that a longer metaphase may be a feature of brain stem cells. Further studies are now needed to find out how the length of time these progenitor cells spend in metaphase affects how chimpanzee and human brains develop; and whether this can help explain why the human brain is so much larger.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Animals / Brain architecture / Cell Biology / Cell division / Cell Proliferation / Cerebral cortex / Cerebral Cortex - embryology / cerebral organoids / chimpanzee / Chimpanzees / Chromosomes / Cognitive ability / Comparative analysis / cortical development / Developmental Biology and Stem Cells / Gene expression / Gene Expression Profiling / Humans / Intravital Microscopy / Laboratory animals / Metaphase / Microscopy, Fluorescence / Mitosis / Neural circuitry / neural stem and progenitor cells / Neural stem cells / Neural Stem Cells - physiology / Neuroimaging / Organoids / Organoids - growth & development / Pan troglodytes / Physiological aspects / Single-Cell Analysis / single-cell RNA-seq / Stem cells