Biology subjects

McCutcheon, C.

Publications and source records attributed to McCutcheon, C..

3 recordsLinked to original sources

bioRxiv2025

Cellular and Immune Adaptations at the Maternal-Fetal Interface in Bats

Bats maintain pregnancy despite extended gestation relative to other small mammals, high fetal investment, recurrent pathogen exposure, and the metabolic demands of flight. These physiological extremes likely drive unique adaptations in placental function and maternal-fetal immune regulation, yet the cellular and molecular basis of these adaptations remains largely unknown. Here, we mapped the cellular landscape of the Jamaican fruit bat (Artibeus jamaicensis) placenta using single-nucleus RNA sequencing (snRNA-seq), integrated with histological and immunohistochemical analyses. We identified diverse trophoblast, stromal, and immune populations at the maternal-fetal interface, including specialized macrophages expressing pregnancy-associated signaling molecules. Trajectory analysis revealed dynamic trophoblast differentiation through proliferative, invasive, and syncytial states. To model these processes in vitro, we derived trophoblast and decidual gland organoids from matched tissues, which recapitulated key in vivo cell types and lineage trajectories. Cross-species transcriptomic comparisons with human and mouse placentas uncovered bat-specific gene programs in trophoblasts, fibroblasts, and immune cells. Notably, bat trophoblast organoids exhibited attenuated antiviral signaling compared to their human counterparts, suggesting species-specific modulation of innate immunity at the maternal-fetal interface. These findings define cellular strategies that support pregnancy under extreme physiological conditions and establish a framework for investigating the evolution of placental adaptations across mammals. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/654282v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@12e7580org.highwire.dtl.DTLVardef@1245751org.highwire.dtl.DTLVardef@e0b9b0org.highwire.dtl.DTLVardef@1bf0694_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO Using single-nucleus RNA sequencing (snRNA-seq) and placental organoids, we reveal unique trophoblast differentiation, immune cell specialization, and expanded stromal populations in Jamaican fruit bat placentas. Cross-species comparisons underscore bat-specific evolutionary adaptations critical for sustaining pregnancy amid extreme metabolic and immunological challenges. C_FIG SummaryPregnancy in bats occurs under a combination of physiological stressors rarely encountered in other mammals, including extended gestation relative to other small mammals, elevated metabolic load, temperature fluctuations associated with flight, and constant microbial exposure. To investigate how the placenta adapts to these challenges, we profiled Jamaican fruit bat (Artibeus jamaicensis) placenta using single-nucleus RNA sequencing and tissue-derived organoid models. This analysis revealed diverse trophoblast, stromal, and immune cell populations with bat-specific transcriptional programs. We identified dynamic trophoblast differentiation trajectories, fibroblasts with hybrid adventitial-neuronal signatures, and macrophages expressing pregnancy-associated molecules typically restricted to trophoblasts. Cross-species comparisons with human and mouse placentas uncovered both conserved cell states and lineage-specific adaptations, providing insight into the evolution of placental function and immune regulation across mammals. HighlightsO_LISingle-nucleus RNA-seq defines cell types and differentiation pathways in the bat placenta C_LIO_LIBat trophoblast and decidua gland organoids recapitulate in vivo lineage trajectories and cell signatures C_LIO_LIBat-specific transcriptional programs revealed across trophoblast, stromal, and immune lineages C_LIO_LIBat trophoblasts exhibit attenuated antiviral responses compared to human counterparts C_LI

developmental biology↗

bioRxiv2024

Defining Cellular Diversity at the Swine Maternal-Fetal Interface Using Spatial Transcriptomics and Organoids

The placenta is a dynamic, embryo-derived organ essential for fetal growth and development. While all eutherian mammals have placentas composed of fetal-derived trophoblasts that mediate maternal-fetal exchange, their anatomical and histological structures vary across species due to evolutionary divergence. Despite the cellular heterogeneity of porcine trophoblasts in vivo, understanding the mechanisms driving porcine placental development has been limited by the lack of in vitro models replicating this heterogeneity. In this study, we derived swine trophoblast organoids (sTOs) from full-term porcine placentas, retaining key transcriptional signatures of in vivo trophoblasts. To identify conserved cell populations, we integrated Visium spatial transcriptomics from mid-gestation porcine placentas with single-cell transcriptomics from sTOs. Spatial transcriptomics revealed novel markers of the porcine uterus and placenta, enabling precise separation of histological structures at the maternal-fetal interface. The integration of tissue and sTO transcriptomics showed that sTOs spontaneously differentiate into distinct trophoblast populations, with conserved gene expression and cell communication programs. These findings demonstrate that sTOs recapitulate porcine placental trophoblast populations, offering a powerful model for advancing placentation research. Our work also provides a spatially resolved whole-transcriptome dataset of the porcine maternal-fetal interface, opening new avenues for discoveries in placental development, evolution, and health across mammals.

developmental biology↗

bioRxiv2020

The impact of exercise intensity on neurophysiological indices of food-related inhibitory control and cognitive control: A randomized crossover event-related potential (ERP) study

Food-related inhibitory control, the ability to withhold a dominant response towards highly palatable foods, influences dietary decisions. Food-related inhibitory control abilities may increase following a bout of aerobic exercise; however, the impact of exercise intensity on both food-related inhibitory control and broader cognitive control processes is currently unclear. We used a high-powered, within-subjects, crossover design to test how relative intensity of aerobic exercise influenced behavioral (response time, accuracy) and neural (N2 and P3 components of the scalp-recorded event-related potential [ERP]) measures of food-related inhibitory and cognitive control. Two hundred and thirteen participants completed three separate conditions separated by approximately one week in randomized order: two exercise conditions (35% [moderate] or 70% [vigorous] of VO2max) and seated rest. Directly following exercise or rest, participants completed a food-based go/no-go task and a flanker task while electroencephalogram data were recorded. Linear mixed models showed generally faster response times (RT) and improved accuracy following vigorous exercise compared to rest, but not moderate-intensity exercise; RTs and accuracy did not differ between moderate intensity exercise and rest conditions. N2 and P3 amplitudes were larger following vigorous exercise for the food-based go/no-go task compared to rest and moderate intensity exercise. There were no differences between exercise conditions for N2 amplitude during the flanker task; however, P3 amplitude was more positive following vigorous compared to rest, but not moderate exercise. Gender did not moderate exercise outcomes. Results suggest improved and more efficient food- related recruitment of later inhibitory control and cognitive control processes following vigorous exercise.

neuroscience↗