Spatiotemporal transcriptomic divergence across human and macaque brain development

Abstract

Human nervous system development is an intricate and protracted process that requires precise spatio-temporal transcriptional regulation. Here we generated tissue-level and single-cell transcriptomic data from up to sixteen brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intra-species (ontogenetic) and inter-species (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.

Transcriptomic and Cellular Decoding of Regional Brain Vulnerability to Neurodevelopmental Disorders

“…Strikingly -in humans, as in mice 34 -these spatial relationships between intrinsic cortical expression of CNV genes, and cortical anatomy changes in CNV carriers could be recovered despite reliance on spatially-comprehensive gene expression data that had been derived from adult brains. Thus, although gene expression landscapes within the brain show profound spatiotemporal dynamism 21 , there appears to be sufficient stability in the topology of gene expression to recover CNV-specific associations over developmental time.…”

Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains

“…Single cell RNA sequencing provides an opportunity to decompose gene expression within brain regions and compare homologous cell types across species [La Manno et al, 2016;Saunders et al, 2018;Tosches et al, 2018;Zeisel et al, 2018]. A single cell level comparison between human and macaque transcriptomes in prenatal and adult dorsolateral prefrontal cortices indeed showed that all detected human cell types had a close homolog in macaques, and vice versa [Zhu et al, 2018]. Furthermore, this study identified genes differentially expressed between humans and macaques in individual cell types.…”

Variation of human neural stem cells generating organizer statesin vitrobefore committing to cortical excitatory or inhibitory neuronal fates

“…In the developing mammalian telencephalon, before neurons are specified, organizer centers emerge to pattern different cortical domains (Geschwind and Rakic, 2013;Grove and Fukuchi-Shimogori, 2003;O'Leary et al, 2007;Sur and Rubenstein, 2005). Recent reports of speciesspecific differences in corticogenesis are often focused on relatively late neurogenic stages where there is an enhanced genesis of superficial neurons in the primate outer subventricular zone (oSVZ) (Namba and Huttner, 2017;Nowakowski et al, 2016;Zhu et al, 2018). However, evolutionary expansion of the cerebral primordium is evident from the earliest stages, even before the onset of corticogenesis, and is already prominent when RGCs produce the first glutamatergic neurons (Bystron et al, 2008;Geschwind and Rakic, 2013).…”