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Gottscho, A. D.

Publications and source records attributed to Gottscho, A. D..

2 recordsLinked to original sources

Comparative phylogeography of lizards (Squamata: Phrynosomatidae) in Baja California and expansion of Callisaurus draconoides within the North American deserts

We examined the comparative phylogeography of five co-distributed lizard complexes (representing four genera within Phrynosomatidae) along the Baja California Peninsula (BCP) in the context of the regions complex geological history. Double-digest restriction-associated-DNA (ddRAD) sequencing was used to collect genome-wide sequence data for 228 peninsular lizards. Using phylogenetic analyses of concatenated loci and population admixture analysis of unlinked SNPs, we identified 24 potential lineages within the five co-distributed complexes. Four of the five complexes exhibited contact zones between lineages at the Isthmus of La Paz, and all five did in the Vizcaino Desert. To generate data for a species tree model, we subsampled two lizards from each of these 24 lineages for use with a target sequence capture (TSC) protocol. The resulting time-calibrated species tree shows that within each genus, the La Paz divergences are older than those across the Vizcaino Desert. A full-likelihood Bayesian comparative phylogeographic approach was also used to test the simultaneous divergence hypothesis for the Isthmus of La Paz and Vizcaino Desert, providing strong support for at least three independent divergence events at each contact zone, thereby rejecting the simultaneous divergence hypothesis. Finally, we demonstrate through expanded geographic sampling (n=142) and ddRAD that zebra-tailed lizards (Callisaurus), in which the most divergent lineages are endemic to the southern BCP, exhibit a clear pattern of Pleistocene range expansion from the northern BCP into the deserts of the western United States and mainland Mexico. The most deeply nested individuals in our tree occur at the northern, eastern, and southeastern range limits in temperate, subtropical, and tropical biomes, respectively. These results collectively highlight the importance of the BCPs tectonic isolation as a driver not only of local or peninsular endemism, but potentially also as a contributing factor to lineage diversification more broadly in the region.

evolutionary biology↗

Characterization of immune cell populations in the tumor microenvironment of colorectal cancer using high definition spatial profiling

Colorectal cancer (CRC) is the second-deadliest cancer in the world, yet a deeper understanding of spatial patterns of gene expression in the tumor microenvironment (TME) remains elusive. Here, we introduce the Visium HD platform (10x Genomics) and use it to investigate human CRC and normal adjacent mucosal tissues from formalin fixed paraffin embedded (FFPE) samples. The first assay available on Visium HD is a probe-based spatial transcriptomics workflow that was developed to enable whole transcriptome single cell scale analysis. We demonstrate highly refined unsupervised spatial clustering in Visium HD data that aligns with the hallmarks of colon tissue morphology and is notably improved over earlier Visium assays. Using serial sections from the same FFPE blocks we generate a single cell atlas of our samples, then we integrate the data to comprehensively characterize the immune cell types present in the TME, specifically at the tumor periphery. We observed enrichment of two pro-tumor macrophage subpopulations with differential gene expression profiles that were localized within distinct tumor regions. Further characterization of the T cells present in one of the samples revealed a clonal expansion that we were able to localize in the tissue using in situ gene expression analysis. In situ analysis also allowed us to perform in-depth characterization of the microenvironment of the clonally expanded T cell population and we identified a third macrophage subpopulation with gene expression profiles consistent with an anti-tumor response. Our study provides a comprehensive map of the cellular composition of the CRC TME and identifies phenotypically and spatially distinct immune cell populations within it. We show that the single cell-scale resolution afforded by Visium HD and the whole transcriptome nature of the assay allows investigations into cellular function and interaction at the tumor periphery in FFPE tissues, which has not been previously possible.

cancer biology↗