Biology subjects

Tyler, T.

Publications and source records attributed to Tyler, T..

4 recordsLinked to original sources

bioRxiv2026

Proliferative Capacity and Neural Lineage Commitment of Muller Glia in the Adult Human Retina

BackgroundThe mammalian retina lacks meaningful regenerative capacity, and degeneration usually leads to irreversible vision loss. Although lower vertebrates regenerate retinal neurons through Muller glia, this capacity has generally been considered absent in humans. This study investigated whether defined humoral cues alone are sufficient to unlock a latent neurogenic program in human Muller cells. MethodsLong-term organotypic retinal cultures were established from 39 adult donors. Cultures were treated with FGF-2 and GSK-3 inhibition to assess proliferation across the peripheral and central retina. Cellular responses were evaluated using single-cell transcriptomics and immunohistochemistry. ResultsFGF-2 treatment and GSK-3 inhibition induced robust proliferation across both peripheral and central retina, with 79.09 {+/-} 6.32% of dividing cells identified as Muller glia, some completing multiple cell cycles. Single-cell transcriptomics revealed activation of progenitor-like and neuronal differentiation pathways, whereas immunohistochemistry demonstrated expression of early and late neuronal markers spanning all major retinal lineages. Newly generated cells expressed markers of cone, rod, bipolar, horizontal, amacrine, and ganglion cell identities, together with evidence of early synaptogenesis. ConclusionsThese findings reveal an intrinsic regenerative potential in adult human Muller glia and show that defined humoral cues can activate a latent neurogenic program in these cells. This may have implications for future vision-restoration strategies in degenerative retinal disease.

neuroscience↗

bioRxiv2021

Spatiotemporal dynamics of human microglia are linked with brain developmental processes across the lifespan

Microglia, the brains resident macrophages, shape neural development and wiring, and are key neuroimmune hubs in the pathological signature of neurodevelopmental disorders. In the human brain, microglial development has not been carefully examined yet, and most of our knowledge derives from rodents. We established an unprecedented collection of 97 postmortem tissues enabling quantitative, sex-matched, detailed analysis of microglial across the human lifespan. We identify the dynamics of these cells in the human telencephalon, describing novel waves in microglial density across gestation and infancy, controlled by a balance of proliferation and apoptosis, which track key neurodevelopmental milestones. These profound changes in microglia are also observed in bulk RNAseq and single-cell RNAseq datasets. This study provides unparalleled insight and detail into the spatiotemporal dynamics of microglia across the human lifespan. Our findings serve as a solid foundation for elucidating how microglia contribute to shaping neurodevelopment in humans.

neuroscience↗

bioRxiv2020

Selective vulnerability of supragranular layer neurons in schizophrenia

Schizophrenia is one of the most wide-spread mental brain disorders with complex and largely unknown etiology. To characterize the impact of schizophrenia at a cellular level, we performed single nucleus RNA sequencing of >190,000 neurons from the dorsolateral prefrontal cortex of patients with schizophrenia and matched controls (7 vs 11, respectively). In addition, to correlate data with cortical anatomy, >100,000 neurons were analyzed topographically by immunohistochemistry in an extended cohort of cases with schizophrenia and controls (10 vs 10). Compositional analysis of RNA sequencing data revealed reduction in relative abundance across all families of GABAergic neurons and a concomitant increase in principal neurons, which was most pronounced for supragranular subtypes (layers 2-3). Moreover, supragranular subtypes of GABAergic interneurons showed most dramatic transcriptomic changes. These results were substantiated by histological analysis, which revealed a reduction in the density of calretinin, calbindin and parvalbumin GABAergic interneurons particularly in layer 2. Common effect of schizophrenia on supragranular neuronal networks was underlined by downregulation of protein processing genes and upregulation of neuronal development/plasticity genes across supragranular subtypes of principal neurons and GABAergic interneurons. In situ hybridization and spatial transcriptomics further confirmed supragranular layer neuron vulnerability, revealing complexity of schizophrenia-affected cortical circuits. These point towards general network impairment within supragranular layers being a core substrate associated with schizophrenia symptomatology.

neuroscience↗

bioRxiv2017

A persistent lack of International representation on editorial boards in biology

The scholars comprising journal editorial boards play a critical role in defining the trajectory of knowledge in their field. Nevertheless, studies of editorial board composition remain rare, especially those focusing on journals publishing research in the increasingly globalized fields of science, technology, engineering, and math (STEM). Using metrics for quantifying the diversity of ecological communities, we quantified international representation on the 1985-2014 editorial boards of twenty-four environmental biology journals. Over the course of three decades there were 3831 unique scientists based in 70 countries that served as editors. The size of the editorial community increased over time - there were 420% more editors serving in 2014 than in 1985 - as did the number of countries in which editors were based. Nevertheless, editors based outside the Global North (the group of economically developed countries with high per capita Gross Domestic Product (GDP) that collectively concentrate most global wealth) were extremely rare. Furthermore, 67.06% of all editors were based in either the USA or UK. Consequently, Geographic Diversity - already low in 1985 - remained unchanged through 2014. We argue that this limited geographic diversity can detrimentally affect the creativity of scholarship published in journals, the progress and direction of research, the composition of the STEM workforce, and the development of science in Latin America, Africa, the Middle East, and much of Asia (i.e., the Global South).

scientific communication and education↗