Biology subjects

Babbitt, C. C.

Publications and source records attributed to Babbitt, C. C..

7 recordsLinked to original sources

bioRxiv2026

Cross-species neural co-culture uncovers metabolic signatures of cellular crosstalk

Primates are distinguished by large brains relative to body size, with humans showing the greatest expansion. This increase in brain size evolved alongside advanced cognitive abilities as well as an elevated energetic demand. Importantly, allometric scaling alone does not explain this increased metabolic requirement, suggesting that other cellular mechanisms may be driving the unique energetic capacity of the human brain. Brain metabolism is critical for neurological function by providing the energy necessary for neuron firing. Much of metabolism in the brain is carried out by astrocytes: a type of glial cell that have long been viewed as passive support cells for neurons. More recent research has highlighted the unique roles of astrocytes in many critical neurological processes; however, it is less understood how astrocytes differ among species. To better characterize this, we developed a cross-species co-culture model of astrocytes and neurons from human or chimpanzee-derived iPSCs. This co-culture system allowed us to assess cell-type specific effects as well as species-specific differences in cellular interactions that may be driving overall differences in brain metabolism. We conducted single-cell RNA-sequencing as well as Seahorse XF Mitochondrial Stress tests and observed that human neural co-cultures are more metabolically active than chimpanzee neural co-cultures. Cross-species co-culture systems also highlight that astrocytes are driving major species differences in metabolism, whereas neurons are highly responsive to astrocytic activity. We conclude that both neurons and astrocytes have evolved differently across primates, and that metabolic interactions between these cell types are key contributors in primate brain evolution.

evolutionary biology↗

bioRxiv2025

Transcriptomic changes across subregions of the primate cerebellum support the evolution of uniquely human behaviors

BackgroundCompared to other primates, humans display unique behaviors including language and complex tool use. These abilities are made possible in part by the cerebellum. This region of the hindbrain, comprising the flocculus, vermis, and lateral hemispheres, has expanded throughout primate evolution, particularly in great apes. Given the cerebellums architecture--differing in connectivity, neuron content, and functions across subregions--examining subregional differences is crucial to understanding its evolutionary trajectory. ResultsWe performed bulk RNA-seq across samples from six primate species, representing 40-50 million years of evolutionary history, across four subregions of the cerebellum (vermis, flocculus, right lateral hemisphere, left lateral hemisphere). We analyzed changes in gene expression with respect to evolutionary relationships via the Ornstein-Uhlenbeck model and found that, on average, 8.5% of orthologous genes are differentially expressed in humans relative to other non-human primates. Subregion-specific gene expression patterns reveal that the primate lateral hemispheres exhibit significant differences in synaptic activity and glucose metabolism, which in turn are highly implicated in neural processing. ConclusionsThis study provides a novel perspective on gene expression divergences across cerebellar subregions in multiple primate species, offering valuable insights into the evolution of this brain structure. Our findings reveal distinct subregional transcriptomic patterns, with the lateral hemispheres emerging as key sites of divergence across the six primate species. The enrichment of genes related to synaptic activity, glucose metabolism, locomotion, and vocalization highlights the cerebellums crucial role in supporting the neural complexity underlying uniquely human and other species-specific primate behaviors.

genomics↗

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↗

bioRxiv2020

Evolutionary variation in MADS-box dimerization affects floral development and protein degradation dynamics

Shifting interactions between MADS-box transcription factors may have been critical in the emergence of the flower, and in floral diversification. However, how evolutionary variation in MADS-box interactions affects the development and evolution of floral form remains unknown. Interactions between B-class MADS-box proteins are variable across the grass family. Here, we test the functional consequences of this evolutionary variability using maize as an experimental system. We found that differential B-class dimerization was associated with subtle, quantitative differences in stamen shape. In contrast, differential dimerization resulted in large-scale changes to protein complex composition and downstream gene expression. Differential dimerization also affected B-class complex abundance, independent of RNA levels. Thus, differential dimerization may affect protein stability. This reveals an important consequence for evolutionary variability in MADS-box interactions, adding complexity to the evolution of developmental gene networks. Our results show that floral development is robust to molecular change, even coding change in a master regulator of development. This robustness may contribute to the evolvability of floral form.

plant 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↗

bioRxiv2017

Mechanosensing of Integrin α6 and EGFR Converges atCalpain 2

Introduction Introduction Materials and Methods Results Discussion Conclusions Author Contributions Conflict of Interest References Carcinoma progression is associated with deposition of ECM that stiffens the local microenvironment [1, 2]. This tissue stiffening results in deposition of additional matrix proteins, initiating a positive feedback loop between cells and the evolving stroma [3]. Cells sense and respond to the stiffness of their environment via RhoA GTPase activation, which feeds back to increase cell contractility via activation of myosin light chain kinase [4]. These ECM-driven changes in cytoskeletal tension regulate motility in a cell-type specific manner [5]. In vi ...

bioengineering↗