Species-specific maturation profiles of human, chimpanzee and bonobo neural cells

Marchetto, Maria C.; Hrvoj-Mihić, Branka; Kerman, Bilal E.; Yu, Diana; Vadodaria, Krishna C.; Linker, Sara B.; Narvaiza, Iñigo; Santos, Renata; Denli, Ahmet M.; Mendes, Ana Cristina; Oefner, Ruth; Cook, Jonathan; McHenry, Lauren; Grasmick, Jaeson Michael; Heard, Kelly J.; Fredlender, Callie; Randolph‐Moore, Lynne; Kshirsagar, Rijul S.; Xenitopoulos, Rea; Chou, Grace; Hah, Nasun; Muotri, Alysson R.; Padmanabhan, Krishnan; Semendeferi, Katerina; Gage, Fred H.

doi:10.7554/elife.37527

Cited by 113 publications

(99 citation statements)

References 54 publications

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“…for example, rat dissociated neurons reach stage 3 after approximately 1.5 days in culture, and cortical development in maturation in mammals ranging from mouse to primate is both faster and less complex than in humans (Dotti, Sullivan, and Banker 1988;Clowry, Molnar, and Rakic 2010;Molnar and Clowry 2012;Silbereis et al 2016;Marchetto et al 2019). We found that human iPSC-derived neurons transition to stage 3 in approximately 7 days, which is consistent with the described prolonged development of human neurons in vivo and in vitro (Grabrucker et al 2009).…”

Section: Development Of Polarized and Functional Human Ipsc-derived Nsupporting

confidence: 86%

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Lindhout

Kooistra

Portegies

et al. 2020

Preprint

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Early neuronal development is a well-coordinated process in which neuronal stem cells differentiate into polarized neurons. This process has been well studied in classical non-human model systems, but to what extent this is recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured human iPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. We found extensive remodeling of the neuron transcriptome and proteome, with altered mRNA expression of ~1,100 genes and different expression profiles of ~1,500 proteins during neuronal differentiation and polarization. We also identified a distinct stage in axon development marked by an increase in microtubule remodeling and apparent relocation of the axon initial segment from the distal to proximal axon. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.(FOM, #16NEPH05, CJW). AUTHOR CONTRIBUTIONSFWL, RK and SP designed the research, conducted experiments, and wrote the article together with LJH. RS conducted and analyzed the mass spectrometry experiments supervised by MA, LJH performed and interpreted the electrophysiology data supervised by CJW, RK and BLS provided and interpreted the RNA sequencing analysis. HDM edited the article. CCH designed the experimental plan, supervised the research and wrote the article.

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Section: Development Of Polarized and Functional Human Ipsc-derived Nsupporting

confidence: 86%

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Lindhout

Kooistra

Portegies

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…This study complements previous research focused on protein-coding changes [4,6] and helps extend the investigation of species-specific differences in cortical development that has so far relied on detailed comparisons between humans and non-human primates [52,[57][58][59][60].…”

Section: Resultssupporting

confidence: 55%

Modern human changes in regulatory regions implicated in cortical development

Moriano

Boeckx

2020

BMC Genomics

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Background: Recent paleogenomic studies have highlighted a very small set of proteins carrying modern humanspecific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to identify derived regulatory changes in the modern human lineage in comparison to Neanderthals/Denisovans. We report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes and are active at early stages of cortical development. Results: We identified 212 genes controlled by regulatory regions harboring modern human changes where Neanderthals/Denisovans carry the ancestral allele. These regulatory regions significantly overlap with putative modern human positively-selected regions and schizophrenia-related genetic loci. Among the 212 genes, we identified a substantial proportion of genes related to transcriptional regulation and, specifically, an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT signaling for the generation and proliferation of intermediate progenitor cells. Conclusions: This study complements previous research focused on protein-coding changes distinguishing our species from Neanderthals/Denisovans and highlights chromatin regulation as a functional category so far overlooked in modern human evolution studies. We present a set of candidates that will help to illuminate the investigation of modern human-specific ontogenetic trajectories.

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“…One study, using 2D and 3D stem cellderived cultures, found that differences in neuronal cell numbers among rodents, non-human primates, and humans could be partially explained by the differences in the presence and length of a developmental stage of cerebral cortex progenitor expansion that was significantly increased in humans [111]. Supporting this finding, two studies found that cellular maturation took longer in humans organoids compared to chimpanzee and bonobo organoids [82,110]. Many upregulated genes and changes in DNA accessibility in these studies were identified as being specific to the developing human brain [82].…”

Section: Evolution Of the Human Brainmentioning

confidence: 96%

“…One other interesting emerging application is to study the evolution of the human brain by comparing cultures derived from human to other non-human primates which share many of the transcriptional programs determining cell type in the developing cerebellar cortex [82,83,110,111]. One study, using 2D and 3D stem cellderived cultures, found that differences in neuronal cell numbers among rodents, non-human primates, and humans could be partially explained by the differences in the presence and length of a developmental stage of cerebral cortex progenitor expansion that was significantly increased in humans [111].…”

Section: Evolution Of the Human Brainmentioning

confidence: 99%

Human in vitro models for understanding mechanisms of autism spectrum disorder

Gordon

Geschwind

2020

Molecular Autism

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Early brain development is a critical epoch for the development of autism spectrum disorder (ASD). In vivo animal models have, until recently, been the principal tool used to study early brain development and the changes occurring in neurodevelopmental disorders such as ASD. In vitro models of brain development represent a significant advance in the field. Here, we review the main methods available to study human brain development in vitro and the applications of these models for studying ASD and other psychiatric disorders. We discuss the main findings from stem cell models to date focusing on cell cycle and proliferation, cell death, cell differentiation and maturation, and neuronal signaling and synaptic stimuli. To be able to generalize the results from these studies, we propose a framework of experimental design and power considerations for using in vitro models to study ASD. These include both technical issues such as reproducibility and power analysis and conceptual issues such as the brain region and cell types being modeled.Early development as a critical period for ASD susceptibility

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Species-specific maturation profiles of human, chimpanzee and bonobo neural cells

Cited by 113 publications

References 54 publications

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Quantitative mapping of transcriptome and proteome dynamics during polarization of human iPSC-derived neurons

Modern human changes in regulatory regions implicated in cortical development

Human in vitro models for understanding mechanisms of autism spectrum disorder

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