Biology subjects

McLaughlin, L.

Publications and source records attributed to McLaughlin, L..

4 recordsLinked to original sources

bioRxiv2026

NetTracer3D Enables User-Friendly Analysis of Diverse Microscopic and Medical 3D Datasets

Recent advances in high-resolution imaging and spatial transcriptomics have enabled reconstruction of complex 3D tissue maps, providing unprecedented insights into cellular connectivity, organization, and tissue architecture. However, standardization challenges hinder integration, sharing, and analysis of these datasets across research communities. We developed NetTracer3D to simplify three-dimensional image analysis across diverse datasets. NetTracer3D is an integrated tool for defining, processing, and sharing 3D tissue maps with standardized data formats and interactive exploration capabilities. It provides three broadly applicable network analysis modalities: Connectivity networks for analyzing functional tissue units or cells connected via secondary structures such as nerves or vasculature; Branch Adjacency and Branchpoint networks for converting branched anatomical structures into analyzable representations; and Proximity networks for grouping structures by spatial relationships to identify cellular organization patterns. We demonstrate several use cases applying NetTracer3D to analyze multidimensional data from CODEX and label free Raman spectroscopy, multiscalar data encompassing subcellular and anatomical scales and a range of modalities. NetTracer3D was able to characterize neural relationships between functional tissue units in human and mouse kidneys and mouse bronchi. Branchpoint networks were used to identify vascular defects in human brain angiogram and define the innervation structure of a lymph node. Finally, we demonstrate how proximity networks characterize the tumor microenvironment in 3D light sheet cancer images and auto-detect cellular neighborhoods in multiplexed 2D CODEX datasets. Beyond network creation, NetTracer3D enables analysis, spatial statistics, and visual analytics tailored for volumetric tissue data. By establishing interoperable formats and analysis workflows, this work provides accessible and reproducible analytical tools for 3D spatial biology, enabling new discoveries of relationships between structure and physiology.

genomics↗

bioRxiv2025

Microglial plasticity governed by state-specific enhancer landscapes

Single-cell transcriptomic studies have identified distinct microglial subpopulations with shared and divergent gene signatures across development, aging and disease. Whether these microglial subsets represent ontogenically separate lineages of cells, or they are manifestations of plastic changes of microglial states downstream of some converging signals is unknown. Furthermore, despite the well-established role of enhancer landscapes underlying the identity of microglia, to what extent histone modifications and DNA methylation regulate microglial state switches at enhancers have not been defined. Here, using genetic fate mapping, we demonstrate the common embryonic origin of proliferative-region-associated microglia (PAM) enriched in developing white matter, and track their dynamic transitions into disease-associated microglia (DAM) and white matter-associated microglia (WAM) states in disease and aging contexts, respectively. This study links spatiotemporally discrete microglial states through their transcriptomic and epigenomic plasticity, while revealing state-specific histone modification profiles that govern state switches in health and disease.

neuroscience↗

bioRxiv2024

Three Dimensional Multiscalar Neurovascular Nephron Connectivity Map of the Human Kidney Across the Lifespan

The human kidney is a vital organ with a remarkable ability to coordinate the activity of up to a million nephrons, its main functional tissue unit (FTU), and maintain homeostasis. We developed tissue processing and analytical methods to construct a 3D map of neurovascular nephron connectivity of the human kidney and glean insights into how this structural organization enables coordination of various functions of the nephron, such as glomerular filtration, solute and water absorption, secretion by the tubules, and regulation of blood flow and pressure by the juxtaglomerular apparatus, in addition to how these functions change across disease and lifespans. Using light sheet fluorescence microscopy (LSFM) and morphometric analysis we discovered changes in anatomical orientation of the vascular pole, glomerular density, volume, and innervation through postnatal development and ageing. The extensive nerve network exists from cortex FTUs to medullary loop of Henle, providing connectivity within segments of the same nephron, and between separate nephrons. The nerves organize glomeruli into discreet communities (in the same network of nerves). Adjacent glomerular communities are connected to intercommunal "mother glomeruli" by nerves, a pattern repeating throughout the cortex. These neuro-nephron networks are not developed in postnatal kidneys and are disrupted in diseased kidneys (diabetic or hydronephrosis). This structural organization likely poises the entire glomerular and juxtaglomerular FTUs to synchronize responses to perturbations in fluid homeostasis, utilizing mother glomeruli as network control centers.

neuroscience↗

bioRxiv2020

Sequential infection with influenza A virus followed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to more severe disease and encephalitis in a mouse model of COVID-19.

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2, a recently emerged coronavirus that rapidly caused a pandemic. Coalescence of this virus with seasonal respiratory viruses, particularly influenza virus is a global health concern. To investigate this, transgenic mice expressing the human ACE2 receptor driven by the epithelial cell cytokeratin-18 gene promoter (K18-hACE2) were first infected with IAV followed by SARS-CoV-2. The host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 only. Infection of mice with each individual virus resulted in a disease phenotype compared to control mice. Although SARS-CoV-2 RNA synthesis appeared significantly reduced in the sequentially infected mice, they exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to singly infected or control mice. The sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by infection with IAV is responsible for the observed inhibition of SARS-CoV-2, however, infection with attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest that the concept of twinfection is deleterious and mitigation steps should be instituted as part of a comprehensive public health response to the COVID-19 pandemic.

microbiology↗