Biology subjects

Crane, J.

Publications and source records attributed to Crane, J..

5 recordsLinked to original sources

bioRxiv2025

Wnt signaling restores evolutionary loss of regenerative potential in Hydra

The regenerative potential of animals varies widely, even among closely-related species. In a comparative study of regeneration across the Hydra genus, we found that while most species exhibit robust whole-body regeneration, Hydra oligactis and other members of the Oligactis clade consistently fail to regenerate their feet. To investigate the mechanisms underlying this deficiency, we analyzed transcriptional responses during head and foot regeneration in H. oligactis. Our analysis revealed that the general injury response in H. oligactis lacks activation of Wnt signaling, a pathway essential for Hydra vulgaris foot regeneration. Notably, transient treatment with a Wnt agonist in H. oligactis triggered a foot-specific transcriptional program, successfully rescuing foot regeneration. Our transcriptional profiling also revealed dlx2 as a likely high-level regulator of foot regeneration, dependent on Wnt signaling activation. Our study establishes a comparative framework for understanding the molecular basis of regeneration and its evolutionary loss in closely-related species.

developmental biology↗

bioRxiv2024

The MET growth signaling complex drives Alzheimers Disease-associated brain pathology in aged Shugoshin 1 mouse cohesinopathy model

The understanding on molecular processes toward Late-onset Alzheimers Disease (LOAD) has been insufficient to design LOAD intervention drugs. Previously, we discovered transgenic genomic instability model mice Sgo1-/+ accumulate cerebral amyloid-beta in old age. We proposed the "amyloid-beta accumulation cycle" hypothesis, in which cytotoxic, mitogenic and aneuploidgenic amyloid can create an autonomous mitotic cycle leading to accumulation of itself. However, the nature of the growth signaling that drives cells toward pathogenic mitotic cycle remained unidentified. In this study, we hypothesized that the aged Sgo1-/+ mice brains would show signs of mitogenic signaling activation, and searched for growth signaling activated in the vicinity of amyloid-beta, with spatial analysis on the cortex and hippocampus of Sgo1-/+ mice in middle-age and old-age. The analysis indicated activations of kinase signaling p42/44 MAPK ERK1/2, AMPK, JNK, Wnt signaling via GSK3 inactivation, as well as increases of p-TAU and other AD biomarkers, PLCG1, EGFR, MET, Neurofibromin and RAS. Immune activation markers CD45 and CD31 were also elevated in the microenvironment. A majority of activated growth signaling components are of the oncogenic MET signaling complex. The discovery supports repurposing of cancer drugs targeting the MET signaling complex and EGFR-RAS-MAPK axis for intervention and/or treatment of genomic instability-driven AD.

neuroscience↗

bioRxiv2023

The ghost of selection past: evolution and conservation relevance of the kakapo color polymorphism

The information contained in population genomic data can tell us much about the past ecology and evolution of species. We leveraged detailed phenotypic and genomic data of nearly all living k[a]k[a]p[o] to understand the evolution of its remarkable feather color polymorphism. The k[a]k[a]p[o] is an endangered and culturally significant parrot endemic to Aotearoa New Zealand, and the green and olive feather colorations are present at similar frequencies in the population. The presence of such a neatly balanced color polymorphism is remarkable because the entire population currently numbers less than 250 birds, which means it has been exposed to severe genetic drift. We dissected the color phenotype, demonstrating that the two colors differ in their light reflectance patterns due to differential feather structure. We used quantitative genomics methods to identify two genetic variants whose epistatic interaction can fully explain the species color phenotype. Our genomic forward simulations show that balancing selection might have been pivotal to establish the polymorphism in the ancestrally large population, and to maintain it during population declines that involved a severe bottleneck. We hypothesize that an extinct apex predator was the likely agent of balancing selection, making the color polymorphism in the k[a]k[a]p[o] a "ghost of selection past".

genomics↗

bioRxiv2022

STOmics-GenX: CRISPR based approach to improve cell identity specific gene detection from spatially resolved transcriptomics

The spatial organisation of cells defines the biological functions of tissue ecosystems from development to disease. Recently, an array of technologies have been developed to query gene expression in a spatial context. These include techniques such as employing barcoded oligonucleotides, single-molecule fluorescence in situ hybridization (smFISH), and DNA nanoball (DNB)-patterned arrays. However, resolution and efficiency vary across platforms and technologies. To obtain spatially relevant biological information from spatially resolved transcriptomics, we combined the Stereo-seq workflow with CRISPRclean technology to develop the STOmics-GenX pipeline. STOmics-GenX not only allowed us to reduce genomic, mitochondrial, and ribosomal reads, but also lead to a [~]2.1-fold increase in the number of detected genes when compared to conventional Stereo-seq (STOmics). Additionally, the STOmics-GenX pipeline resulted in an improved detection of cell type specific genes, thereby improving cellular annotations. Most importantly, STOmics-GenX allowed for enhanced detection of clinically relevant biomarkers such as Alpha-fetoprotein (AFP), enabling the identification of two spatially distinct subsets of hepatocytes in hepatocellular carcinoma tissue. Thereby, combining CRISPRclean technology with STOmics not only allowed improved gene detection but also paved the way for spatial precision oncology by improved detection of clinically relevant biomarkers.

molecular biology↗

bioRxiv2022

Sirtuin gene isoforms and genomic sequences of mouse and humans: Divergence across species

BackgroundThere are seven sirtuin genes in the mammalian genome. Each sirtuin gene contains multiple exons, and is likely to undergo alternative splicing, thereby increasing sirtuin gene diversity. Since the alternatively spliced isoforms tend to increase with advancing age, it is important to study the effect of sequence change on isoform function. Additionally, the divergence of isoform patterns between human and mouse will help us to properly interpret the findings from animal models, especially in age-related studies. Recently, more than 20 human sirtuin isoforms have been identified, but whether the mouse genome might have similar isoforms remains incompletely established. MethodsThe mRNA, protein and genomic DNA sequences of mouse sirtuin genes, as well as the transcription factor binding sites, including that of SRF, were analyzed. A cellular stress model with serum deprivation and restoration was used to reflect the blood supply and nutrients level changes in the ischemia and reperfusion condition, and the expression of sirtuin isoform was assessed. ResultsHere, we report the identification of 15 mouse sirtuin isoforms, of which over half have not been previously reported. Exon skipping was the main event, which led to domain losses in the nuclear localization signal, nucleolar localization signal, and/or the mitochondrial targeting sequence among sirtuin isoforms. Among 7 sirtuin genes, 6 mouse sirtuin genes had different exon numbers versus that of human sirtuin genes. Only the sirtuin-2 gene had the same number of exons in both human and mouse. However, there were differences in the sirtuin-2 gene isoforms and the regulatory domains between the two species. The expression of sirtuin gene isoforms under serum stress was also different. ConclusionsAlternative splicing increases both sirtuin transcriptome and proteome diversity. However, the sirtuin isoforms were not well conserved between human and mouse, which should be taken into consideration when extrapolating animal studies for human physiology and pathology. Our results will help to elucidate the role of sirtuin genes in the regulation of cellular stress response, including ischemia and reperfusion. We propose that the existence of the CArG and CArG-like sequences in sirtuin genes may imply a role for SRF in the sirtuin family transcriptional regulation.

genetics↗