Biology subjects

Sherman, C.

Publications and source records attributed to Sherman, C..

4 recordsLinked to original sources

bioRxiv2025

Diet links gut chemistry with cancer risk in C57Bl/6 mice and human colorectal cancer patients

The gastrointestinal tract is a complex ecosystem in which host tissues, microbial communities, and dietary inputs interact to shape metabolic outputs and epithelial homeostasis. Western-style diets, characterized by high fat and protein and low micronutrient content, represent a sustained ecological perturbation linked to colorectal cancer (CRC), yet specific mechanisms that impact risk remain poorly defined. Here, using a purified Western-style diet (NWD1) that induces sporadic intestinal and colon tumors in wild-type C57BL/6 mice we demonstrate how chronic dietary disturbance restructures gut community composition and sulfur metabolism, and how these changes modulate intestinal stem cell responses. Mice fed NWD1 for 24 weeks exhibited consistent shifts in ecosystem function, including a threefold increase in fecal sulfide production (P < 0.00001) and expansion of Erysipelotrichaceae family taxa. This altered chemical landscape associates with increased expression of mitochondrial sulfide oxidation pathways in Lgr5hi intestinal stem cells. Meta-analysis of human CRC cohorts revealed concordant enrichment of Erysipelotrichaceae, alongside established CRC-associated taxa such as Solobacterium moorei, indicating conserved ecological signatures across systems. Together, these findings support a model in which the Western-style diet drives a persistent shift in gut ecosystem structure and function toward a sulfide producing state that challenges epithelial homeostasis, with conserved microbial and metabolic configurations emerging prior to overt disease in mouse models.

cancer biology↗

bioRxiv2024

Sensitivity to photoperiod is a complex trait in Camelina sativa

Day neutrality, or insensitivity to photoperiod (day length), is an important domestication trait in many crop species. Although the oilseed crop Camelina sativa has been cultivated since the Neolithic era, day-neutral accessions have yet to be described. We sought to leverage genetic diversity in existing germplasms to identify C. sativa accessions with low photoperiod sensitivity for future engineering of this trait. We quantified variation in the photoperiod response across 161 accessions of C. sativa by measuring hypocotyl length of four-day-old seedlings grown in long-day and short-day conditions, finding wide variation in photoperiod response. Similarly, soil-grown adult plants from selected accessions showed variation in photoperiod response in several traits; however, photoperiod responses in seedling and adult traits were not correlated, suggesting complex mechanistic underpinnings. Although RNA-seq experiments of the reference accession Licalla identified several differentially regulated Arabidopsis syntelogs involved in photoperiod response, including COL2, FT, LHY and WOX4, expression of these genes in the accessions did not correlate with differences in their photoperiod sensitivity. Taken together, we show that all tested accessions show some degree of photoperiod response, and that this trait is likely complex, involving several and separable seedling and adult traits. Significance StatementDay neutrality (photoperiod insensitivity) is a common trait in domesticated crops; however, the ancient oilseed crop Camelina sativa has remained photoperiod-sensitive, which likely limits seed yields. Here, we show that photoperiod sensitivity is conserved across many C. sativa cultivars, albeit to different degrees, and we establish that photoperiod sensitivity is a complex trait, which will require genetic engineering to achieve day neutrality.

plant biology↗

bioRxiv2024

Single nucleus transcriptomics supports a role for CCNA2-induced human adult cardiomyocyte cytokinesis

Cyclin A2 (CCNA2), a master cell cycle regulator silenced in postnatal cardiomyocytes, promotes cardiac repair in animal models. However, its effect on cytokinesis in adult human cardiomyocytes remains unknown. We engineered a replication-deficient adenoviral vector encoding human CCNA2 under the cardiac Troponin T promoter and delivered it to freshly isolated cardiomyocytes from adult human hearts. Time-lapse live imaging revealed induction of complete cytokinesis with preservation of sarcomeres and calcium mobilization in redifferentiated daughter cardiomyocytes. To uncover underlying transcriptional mechanisms, single-nucleus transcriptomics of CCNA2-transgenic versus non-transgenic mouse hearts identified a cardiomyocyte subpopulation enriched for cytokinesis, proliferative, and reprogramming genes. Ultra-deep bulk RNA sequencing of adult and fetal human hearts further highlighted reprogramming pathways relevant to CCNA2-induced effects. Together, these findings demonstrate that CCNA2 can reinitiate cytokinesis in adult human cardiomyocytes and illuminate conserved molecular programs, supporting its promise as a regenerative gene therapy for the heart. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/583057v7_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@b9cfa9org.highwire.dtl.DTLVardef@f0720eorg.highwire.dtl.DTLVardef@1d020b2org.highwire.dtl.DTLVardef@112c28b_HPS_FORMAT_FIGEXP M_FIG C_FIG CCNA2 Induces Cytokinesis and Drives Proliferation and Reprogramming of Adult Cardiomyocytes: An Integrative Transcriptomic Analysis across Human and Mouse Models.

cell biology↗

bioRxiv2020

Inherent population structure determines the importance of filtering parameters for reduced representation sequencing analyses

As technological advancements enhance our ability to study population genetics, we must understand how the intrinsic properties of our datasets influence the decisions we make when designing experiments. Filtering parameter thresholds, such as call rate and minimum minor allele frequency (MAF), are known to affect inferences of population structure in reduced representation sequencing (RRS) studies. However, it is unclear to what extent the impacts of these parameter choices vary across datasets. Here, we reviewed literature on filtering choices and levels of genetic differentiation across RRS studies on wild populations to highlight the diverse approaches that have been used. Next, we hypothesized that choices in filtering thresholds would have the greatest impact when analyzing datasets with low levels of genetic differentiation between populations. To test this hypothesis, we produced seven simulated RRS datasets with varying levels of population structure, and analyzed them using four different combinations of call rate and MAF. We performed the same analysis on two empirical RRS datasets (low or high population structure). Our simulated and empirical results suggest that the effects of filtering choices indeed vary based on inherent levels of differentiation: specifically, choosing stringent filtering choices was important to detect distinct populations that were slightly differentiated, but not those that were highly differentiated. As a result, experimental design and analysis choices need to consider attributes of each specific dataset. Based on our literature review and analyses, we recommend testing a range of filtering parameter choices, and presenting all results with clear justification for ultimate filtering decisions used in downstream analyses.

bioinformatics↗