Biology subjects

Cotter, D.

Publications and source records attributed to Cotter, D..

4 recordsLinked to original sources

bioRxiv2026

Full-Term and Preterm Differences in Human Brain Functional Connectivity Development Across Birth

We possess a limited understanding of how preterm and full-term brains develop during the earliest stages of life, from the fetal to neonatal period, and how they respond to the birth transition. Here, we characterize brain resting-state functional connectivity (RSFC) using over 1000 longitudinal fetal and infant functional MRI scans from 21 to 52 post-conception weeks across birth. By mapping the developmental trajectory of RSFC across this window, we unveil marked divergences in developmental patterns between preterm- and term-born brains at both the global and network levels. When aligned by birth, the full-term group exhibit generally higher RSFC than the preterm group. For selected between-network connections with a significant prematurity effect, full-term cases demonstrate an overall increase in RSFC across age, whereas preterm cases show minimal change or even a decrease in connectivity of these systems. In contrast, when aligned by postconceptional age, the preterm group shows an accelerated increase in RSFC between 30 and 40 weeks. Across comparisons, mode of delivery and sex showed minimal influence on these trajectories. These findings offer novel insight into how prematurity and early exposure to the extrauterine environment alter the developmental trajectories of large-scale neural networks, advancing our understanding of both typical and preterm brain development.

neuroscience↗

bioRxiv2024

Single-cell spatial mapping reveals alteration of cell type composition and tissue microenvironment during early colorectal cancer formation

Familial adenomatous polyposis (FAP) is a rare, hereditary syndrome that raises the risk of developing colorectal cancer (CRC). This disease model is well suited for studying the early stages of malignant transformation. Our spatial CODEX experiments reveal that, in contrast to normal mucosa, FAP mucosa, pre-cancer polyps and colorectal cancers exhibit substantial alterations in the cell type composition and tissue microenvironment. These early alterations include: an increase in the population of cancer-associated fibroblasts (CAFs), and the inhibition of tumor infiltrated lymphocytes and cell-adhesion protein by CAFs, the transformation of memory T cells into regulatory T cells, nuclear translocation of beta-catenin from the cell membrane, a decrease in the M1:M2 macrophage ratio, a notable increase in angiogenesis events. Our studies define the early stem cell, stromal, and immune steps of colorectal cancer and may benefit early detection, and therapeutic intervention.

cancer biology↗

bioRxiv2021

High Resolution Single Cell Maps Reveals Distinct Cell Organization and Function Across Different Regions of the Human Intestine

The colon is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota, and affects overall health. To better understand its organization, functions, and its regulation at a single cell level, we performed CODEX multiplexed imaging, as well as single nuclear RNA and open chromatin assays across eight different intestinal sites of four donors. Through systematic analyses we find cell compositions differ dramatically across regions of the intestine, demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighborhoods and communities highlighting distinct immunological niches present in the intestine. We also map gene regulatory differences in these cells suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation, and organization for this organ, and serve as an important reference map for understanding human biology and disease.

genomics↗

bioRxiv2020

Adolescent-onset and adult-onset schizophrenia: reduced ribosomal protein expression via mTOR signalling in patient-derived olfactory cells

Schizophrenia is a heterogeneous disorder associated with many genetic and environmental risk factors that could affect brain development. It is unknown whether adolescent-onset and adult-onset schizophrenia have similar aetiology. To address this we used discovery-based proteomics to find proteins differentially expressed in olfactory neurosphere-derived cells from adolescents with schizophrenia compared to age- and gender-matched healthy controls. Of 1638 proteins identified, 241 were differentially expressed in patient cells, with significant down-regulation of ribosomal and cytoskeletal proteins, and dysregulation of protein synthesis pathways. We then re-analysed our previous adult-onset proteomic data to compare directly with adolescent-onset protein expression. Schizophrenia-associated protein expression in adult-onset patients was remarkably similar to adolescent-onset patients. To increase sample size and power we combined the two datasets for a bioinformatic meta-analysis. Schizophrenia-associated protein expression indicated significant downregulation of the mTOR signalling pathway, which regulates protein synthesis, indicated by the reduced expression of all ribosomal proteins and other mTOR-dependent proteins: RPS6, VIM, LDHB and PPP2R1A. A protein-protein interaction network built from differentially expressed proteins in the combined dataset was significantly associated with schizophrenia-associated risk genes and with proteins regulating neural stem cell differentiation, cell adhesion and growth cones in the developing brain. This study demonstrates that despite the divergent age of onset, the proteomes of olfactory neural stem cells of adolescent- and adult-onset patients are remarkably similar. The dysregulated proteins in patient cells form a tightly interconnected protein-protein interaction network associated with mTOR signalling, protein translation, neurogenesis and axon growth - all key components of brain development.

neuroscience↗