Dataset Information

A cross-species proteomic map reveals neoteny of human synapse development.

ABSTRACT: The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood^1,2. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons reveal that human PSDs mature about two to three times slower than those of other species and contain higher levels of Rho guanine nucleotide exchange factors (RhoGEFs) in the perinatal period. Enhancement of RhoGEF signalling in human neurons delays morphological maturation of dendritic spines and functional maturation of synapses, potentially contributing to the neotenic traits of human brain development. In addition, PSD proteins can be divided into four modules that exert stage- and cell-type-specific functions, possibly explaining their differential associations with cognitive functions and diseases. Our proteomic map of synapse development provides a blueprint for studying the molecular basis and evolutionary changes of synapse maturation.

SUBMITTER: Wang L

PROVIDER: S-EPMC10576238 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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A cross-species proteomic map reveals neoteny of human synapse development.

Wang Li L Pang Kaifang K Zhou Li L Cebrián-Silla Arantxa A González-Granero Susana S Wang Shaohui S Bi Qiuli Q White Matthew L ML Ho Brandon B Li Jiani J Li Tao T Perez Yonatan Y Huang Eric J EJ Winkler Ethan A EA Paredes Mercedes F MF Kovner Rothem R Sestan Nenad N Pollen Alex A AA Liu Pengyuan P Li Jingjing J Piao Xianhua X García-Verdugo José Manuel JM Alvarez-Buylla Arturo A Liu Zhandong Z Kriegstein Arnold R AR

Nature 20230913 7981

The molecular mechanisms and evolutionary changes accompanying synapse development are still poorly understood<sup>1,2</sup>. Here we generate a cross-species proteomic map of synapse development in the human, macaque and mouse neocortex. By tracking the changes of more than 1,000 postsynaptic density (PSD) proteins from midgestation to young adulthood, we find that PSD maturation in humans separates into three major phases that are dominated by distinct pathways. Cross-species comparisons revea ...[more]

PMID: 37704727

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Project description:This dataset consists of single-cell RNA-seq (10X) data from healthy, adult human and pig pancreatic islets. Pancreatic islets of Langerhans secrete hormones to regulate systemic glucose levels. Emerging evidence suggests that islet cells are functionally heterogeneous to allow a fine-tuned and efficient endocrine response to physiological changes. A precise description of the molecular basis of this heterogeneity, in particular linking animal models to human islets, is an important step towards identifying the factors critical for endocrine cell function in physiological and pathophysiological conditions. In this study, we used single-cell RNA sequencing to profile more than 50’000 endocrine cells isolated from healthy human, porcine and murine pancreata and characterize transcriptional heterogeneity and evolutionary conservation of those cells across the three species. We systematically delineated endocrine cell types and α- and β-cell heterogeneity through prior knowledge- and data-driven gene sets shared across species, which altogether capture common and differential cellular properties, transcriptional dynamics and putative driving factors of state transitions. We showed that global endocrine expression profiles correlate, and that critical identity and functional markers are shared between species, while only approximately 20% of cell-type enriched expression is conserved. We resolved distinct human α- and β-cell states that form continuous transcriptional landscapes. These states differentially activate maturation and hormone secretion programs, which are related to regulatory hormone receptor expression, signaling pathways and different types of cellular stress responses. Finally, we mapped mouse and pig cells to the human reference and observed that the spectrum of human α- and β-cell heterogeneity and aspects of such functional gene expression are better recapitulated in the pig than mouse data. Here, we provide a high-resolution transcriptional map of healthy human islet cells and their murine and porcine counterparts, which is easily queryable via an online interface. This comprehensive resource informs future efforts that focus on pancreatic endocrine function, failure and regeneration, and enables to assess molecular conservation in islet biology across species for translational purposes.

Dataset Information

A cross-species proteomic map reveals neoteny of human synapse development.

Publications

A cross-species proteomic map reveals neoteny of human synapse development.

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