Biology subjects

Ahlgren, U.

Publications and source records attributed to Ahlgren, U..

3 recordsLinked to original sources

bioRxiv2023

Illuminating the complete β-cell mass of the human pancreas - signifying a new view on the islets of Langerhans

Pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis, but critical information regarding their mass, distribution and composition is lacking within a whole organ context. Here, a new 3D imaging pipeline was applied to generate a first complete account of the insulin-producing islets throughout the human pancreas at a microscopic resolution and within a maintained spatial 3D context. These data show that human islets are far more heterogenous than previously accounted for with regards to their size distribution and cellular make up. By deep tissue 3D imaging, this in-depth study demonstrates that 50% of the human insulin-expressing islets are virtually devoid of glucagon-producing a-cells, an observation with significant implications for both experimental and clinical research. One Sentence Summary: New islet heterogeneity identified in the human pancreas

cell biology↗

bioRxiv2022

An MR-based brain template and atlas for optical projection tomography and light sheet fluorescence microscopy

Optical projection tomography (OPT) and light sheet fluorescence microscopy (LSFM) are high-resolution optical imaging techniques operating in the mm-cm range, ideally suited for ex vivo 3D whole mouse brain imaging. Although these techniques exhibit high sensitivity and specificity for antibody-labeled targets, the provided anatomical information remains limited. To allow anatomical mapping of fluorescent signal in whole brain, we developed a novel magnetic resonance (MR) - based template with its associated tissue priors and atlas labels, specifically designed for brains subjected to tissue processing protocols required for 3D optical imaging. We investigated the effect of tissue pre-processing and clearing on brain size and morphology and developed optimized templates for BABB/Murrays clear (OCUM) and DBE/iDISCO (iOCUM) cleared brains. By creating optical-(i)OCUM fusion images using our mapping procedure, we localized dopamine transporter and translocator protein expression and tracer innervation from the eye to the lateral geniculate nucleus of thalamus and superior colliculus. These fusion images allowed for precise anatomical identification of fluorescent signal in discrete brain areas. As such, these templates enable applications in a broad range of research areas integrating optical 3D brain imaging by providing an MR template for cleared brains.

neuroscience↗

bioRxiv2021

Whole-brain fluorescence-MRI coregistration for precise anatomical mapping of virus infection

Viral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combined multimodal imaging (cm-nm scale) with single nuclei RNA- sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar-/-) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection was imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection was limited to grey matter of sensory systems in wildtype mice, but extended into white matter, meninges and choroid plexus in Ifnar-/-mice. Cells in wildtype displayed strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+NK cells, whereas in Ifnar-/-, the absence of this response contributed to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.

microbiology↗