Biology subjects

Laskaratos, A.

Publications and source records attributed to Laskaratos, A..

3 recordsLinked to original sources

bioRxiv2024

Identification of perturbation-responsive regions and genes in comparative spatial transcriptomics atlases

We introduce Vespucci, a machine-learning method to identify perturbation-responsive regions, genes and gene programs within comparative spatial transcriptomics atlases. We validate Vespucci on simulated and published datasets and show that it outperforms 19 published computational methods for spatial transcriptomics. We apply Vespucci to expose the spatial organization of gene programs activated by therapies that guide repair of the injured spinal cord.

bioinformatics↗

bioRxiv2024

THE NEURONAL ARCHITECTURE OF AUTONOMIC DYSREFLEXIA

Autonomic dysreflexia is a life-threatening medical condition characterized by episodes of uncontrolled hypertension that occur in response to sensory stimuli after spinal cord injury (SCI)1-7. The fragmented understanding of the mechanisms underlying autonomic dysreflexia hampers the development of therapeutic strategies to manage this condition, leaving people with SCI at daily risk of heart attack and stroke8-18. Here, we expose the complete de novo neuronal architecture that develops after SCI and causes autonomic dysreflexia. In parallel, we uncover a competing, yet overlapping neuronal architecture activated by epidural electrical stimulation of the spinal cord that safely regulates blood pressure after SCI. The discovery that these adversarial neuronal architectures converge onto a single neuronal subpopulation provided a blueprint for the design of a mechanism-based intervention that reversed autonomic dysreflexia in mice, rats, and humans with SCI. These results establish a path for the effective treatment of autonomic dysreflexia in people with SCI.

neuroscience↗

bioRxiv2023

The Tabulae Paralytica: Multimodal single-cell and spatial atlases of spinal cord injury

Here, we introduce the Tabulae Paralytica--a compilation of four atlases of spinal cord injury (SCI) comprising a single-nucleus transcriptome atlas of half a million cells; a multiome atlas pairing transcriptomic and epigenomic measurements within the same nuclei; and two spatial transcriptomic atlases of the injured spinal cord spanning four spatial and temporal dimensions. We integrated these atlases into a common framework to dissect the molecular logic that governs the responses to injury within the spinal cord. The Tabulae Paralytica exposed new biological principles that dictate the consequences of SCI, including conserved and divergent neuronal responses to injury; the priming of specific neuronal subpopulations to become circuit-reorganizing neurons after injury; an inherent trade-off between neuronal stress responses and the activation of circuit reorganization programs; the necessity of reestablishing a tripartite neuroprotective barrier between immune-privileged and extra-neural environments after SCI; and a catastrophic failure to form this barrier in old mice. We leveraged the Tabulae Paralytica to develop a rejuvenative gene therapy that reestablished this tripartite barrier, and restored the natural recovery of walking after paralysis in old mice. The Tabulae Paralytica provides an unprecedented window into the pathobiology of SCI, while establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

genomics↗