Biology subjects

Cisneros, I.

Publications and source records attributed to Cisneros, I..

4 recordsLinked to original sources

bioRxiv2025

Early epigenetic priming of regeneration studied with a novel transgenic epigenetic reporter

Tissue regeneration requires previously differentiated cells to regain developmental plasticity. However, the upstream mechanisms initiating this process remain poorly understood. Here, we leverage a novel "EpiTag" transgenic zebrafish reporter line that enables real-time visualization of epigenetic silencing and activation to identify and carry out a comprehensive multi-omics analysis of cells undergoing epigenetic reprogramming during caudal fin regeneration. EpiTag GFP expression is transiently activated in cells contributing to regeneration between 12 to 16 hours post amputation (hpa), preceding the expression of canonical blastema markers. Single-cell RNA-seq reveals that GFP+ cells are restricted to regeneration-competent lineages such as pre-osteoblasts, proliferating cells, and wound epithelium. Integrated bulk RNA-seq, time-course RNA-seq, ATAC-seq, and bisulfite-seq on FACS-isolated GFP+ cells uncovers an early gene expression module enriched for chromatin regulators and a late gene expression module enriched for morphogenesis genes. Chromatin accessibility and DNA methylation changes are strongly associated with these late-expressed genes, suggesting epigenetic priming. We identify a number of epigenetic factors upregulated in the early gene expression module and show that ruvbl1 and ruvbl2, components of ATP-dependent chromatin remodeling complexes, are required for proper regeneration in both adult fins and larval tails. Our results establish EpiTag transgenics as a powerful in vivo tool for studying epigenetic reprogramming and highlight early chromatin remodeling events that enable activation of regenerative gene expression programs.

genomics↗

bioRxiv2024

A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. Surviving mice showed no detectable viral RNA in the brain and minimal neuroinflammation post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and reduced levels of genes associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent T helper 1 prone cellular immune responses and high neutralizing antibodies against Delta and Omicron variants in the periphery for months post-acute infection. Overall, infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long COVID patients and may be useful for future assessment of the efficacy of vaccines and therapeutics against SARS-CoV-2 variants.

microbiology↗

bioRxiv2022

Divergent expression of aristaless1 and aristaless2 is associated with embryonic appendage and pupal wing development in butterflies

Aristaless is a major regulator of developmental processes. It is well known for its role during appendage specification and extension across animals. Butterflies and moths have two copies of aristaless, aristaless1 (al1) and aristaless2 (al2), as a result of a gene duplication event. Previous work in Heliconius has shown that both copies appear to have novel functions related to wing color patterning. Here we expand our knowledge on the expression profiles associated with both ancestral and novel functions of Al1 across embryogenesis and wing pigmentation. Furthermore, we characterize Al2 expression, providing a comparative framework for understanding the role of gene duplicates in novel and ancestral roles. Our work shows that both Al1 and Al2 expression are associated with developing sensory appendages (leg, mouth, spines, and eyes) in embryos. Interestingly, Al1 appears to show higher expression earlier in embryogenesis while the highest levels of Al2 expression are shifted to later stages of embryonic development. Furthermore, Al1 localization appears extranuclear while Al2 co-localizes tightly with nuclei earlier, and then also expands outside the nucleus later in development. We observed similar cellular expression patterns for Al1 and Al2 in pupal wings when examining their roles in pigmentation. We also describe, for the first time, how Al1 localization appear to correlates with zones of Anterior/Posterior elongation of the body during embryonic growth, showcasing a possible new function related to Aristaless previously described role in appendage extension. Overall, these data suggest similar developmental roles associated with the extension/formation of specific appendages for both duplicates. However, we describe that such functions might be regulated by spatially and temporally complex patterns of expression for al1 and al2. This work expands our knowledge of Aristaless function and expression following gene duplication and the implications of the duplication on butterfly development. Finally, and more fundamentally, our study helps clarify principles behind sub-functionalization and gene expression evolution associated with developmental functions following gene duplication events.

developmental biology↗

bioRxiv2020

Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions

Antibody neutralization is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. These pseudovirions provide a practical means of assessing immune responses under laboratory conditions consistent with biocontainment level 2.

microbiology↗