Biology subjects

Zintel, T. M.

Publications and source records attributed to Zintel, T. M..

4 recordsLinked to original sources

bioRxiv2022

A single-cell multi-omic atlas spanning the adult rhesus macaque brain

Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Altogether, we profiled 2.58M transcriptomes and 1.59M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19M candidate regulatory elements, many novel, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell-type-specific manner. Together, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.

neuroscience↗

bioRxiv2021

Tempo and mode of gene expression evolution in the brain across Primates

Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species 1,2. Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date e.g. 3,4. To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-Seq data from four brain regions in an unprecedented eighteen species. Here we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our sample that represents an unprecedented 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size and found several with signals of positive selection in their regulatory regions. Our study extensively broadens the context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for study of genetic regulation of brain development and evolution.

evolutionary biology↗

bioRxiv2020

Astrocytes drive divergent metabolic gene expression in humans and chimpanzees

The human brain utilizes [~] 20% of all of the bodys metabolic resources, while chimpanzee brains use less than 10%. Although previous work shows significant differences in metabolic gene expression between the brains of primates, we have yet to fully resolve the contribution of distinct brain cell types. To investigate cell-type specific interspecies differences in brain gene expression, we conducted RNA-Seq on neural progenitor cells (NPCs), neurons, and astrocytes generated from induced pluripotent stem cells (iPSCs) from humans and chimpanzees. Interspecies differential expression (DE) analyses revealed that twice as many genes exhibit DE in astrocytes (12.2% of all genes expressed) than neurons (5.8%). Pathway enrichment analyses determined that astrocytes, rather than neurons, diverged in expression of glucose and lactate transmembrane transport, as well as pyruvate processing and oxidative phosphorylation. These findings suggest that astrocytes may have contributed significantly to the evolution of greater brain glucose metabolism with proximity to humans.

evolutionary biology↗

bioRxiv2019

Chimpanzee fibroblasts exhibit greater adherence and migratory phenotypes than human fibroblasts

Background and objectivesPrevious work has identified that gene expression differences in cell adhesion pathways exist between humans and chimpanzees. Here, we used a comparative cell biology approach to assay interspecies differences in cell adhesion phenotypes in order to better understand the basic biological differences between species epithelial cells that may underly the organism-level differences we see in wound healing and cancer. MethodologyWe used skin fibroblast cell lines from humans and chimpanzees to assay cell adhesion and migration. We then utilized published RNA-Seq data from the same cell lines exposed to a cancer / wound-healing mimic to determine what gene expression changes may be corresponding to altered cellular adhesion dynamics between species. ResultsThe functional adhesion and migration assays revealed that chimpanzee fibroblasts adhered sooner and remained adherent for significantly longer and move into a "wound" at faster rate than human fibroblasts. The gene expression data suggest that the enhanced adhesive properties of chimpanzee fibroblasts may be due to chimpanzee fibroblasts exhibiting significantly higher expression of cell and focal adhesion molecule genes than human cells, both during a wound healing assay and at rest. Conclusions and implicationsChimpanzee fibroblasts exhibit stronger adhesion and greater cell migration than human fibroblasts. This may be due to divergent gene expression of focal adhesion and cell adhesion molecules, such as integrins, laminins, and cadherins, as well as ECM proteins like collagens. This is one of few studies demonstrating that these divergences in gene expression between closely related species can manifest in fundamental differences in cell biology. Our results provide better insight into species-specific cell biology phenotypes and how they may influence more complex traits, such as cancer metastasis and wound healing.

evolutionary biology↗