Biology subjects

Ahuna, K.

Publications and source records attributed to Ahuna, K..

3 recordsLinked to original sources

bioRxiv2025

Differential activation of p53-Lamin A/C and p16-RB mediated senescence pathways in trophoblast from pregnancies complicated by type A2 Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) increases maternal risks such as hypertension and future type 2 diabetes while also contributing to fetal complications such as large-for-gestational-age infants and stillbirth. The placenta which is crucial for fetal development, exhibits structural and functional changes in GDM, but the impact of these alterations on placental trophoblast function remains unclear. During their differentiation villous cytotrophoblast display several characteristics of senescent cells however the role of senescence pathways in placental function remains unexplored in GDM. Here we investigate whether placental senescence pathways are altered in GDM, utilizing term villous tissue and primary trophoblasts to assess molecular changes, and determined fetal sex-based differences. Our data suggest that both p21 and p16 mediated senescence pathways are activated during trophoblast differentiation and are dysregulated in GDM placenta in a sexually dimorphic manner. We also provide evidence for increased activation of p53-Lamin A/C and p16-RB pathways in trophoblast from GDM placentas. Reduced expression of p21 and its downstream effects on GCM1 expression and {beta}hCG secretion outline how altered physiological senescence can affect trophoblast differentiation and function. This is a seminal study highlighting how placental senescence pathways are altered in pregnancies complicated by GDM.

cell biology↗

bioRxiv2022

A Genome Scale Transcriptional Regulatory Model of the Human Placenta

Gene regulation is essential to placental function and fetal development. We report a genome-scale transcriptional regulatory network (TRN) of the human placenta built using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out of sample R2 value greater than 0.25 for 74% of target genes. We performed siRNA knockdowns of 4 TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for 3 of the 4 TFs. Our final model contained 113,158 interactions across 391 TFs and 7,712 target genes and is publicly available. We identified six TFs which were significantly enriched as regulators for genes previously associated with preterm birth.

systems biology↗

bioRxiv2019

Optogenetic reactivation of prefrontal social memory trace mimics social buffering of fear

Social buffering occurs when the presence of a companion attenuates the physiological and/or behavioral effects of a stressful or fear-provoking event. It represents a way in which social interactions can immediately and potently modulate behavior. As such, social buffering is one mechanism by which strong social support increases resilience to mental illness. While the behavioral and neuroendocrine impacts of social buffering are well studied in multiple species, including humans, the neuronal bases of this behavioral phenomenon remain largely unexplored. Previous work has shown that the infralimbic prefrontal cortex (IL-PFC) is important for processing social information and, in separate studies, for modulating fear and anxiety. Thus, we hypothesized that socially-active cells within the IL-PFC may integrate social information to modulate fear responsivity. To test this hypothesis, we employed social buffering paradigms in male and female mice. Similar to prior studies in rats, we found that the presence of a cagemate reduced freezing in fear and anxiety-provoking contexts. In accordance with previous work, we demonstrated that interaction with a novel or familiar conspecific induces activity in the IL-PFC as evidenced by increased immediate early gene (IEG) expression. We then utilized an activity-dependent tagging murine line, the ArcCreERT2 mice, to express channelrhodopsin (ChR2) in neurons active during the social encoding of a new cagemate. We found that optogenetic reactivation of these socially-active neuronal ensembles phenocopied the effects of cagemate presence in male and female mice in learned and innate fear contexts without being inherently rewarding or altering locomotion. These data suggest that a social neuronal ensemble within the IL-PFC may contribute to social buffering of fear. These neurons may represent a novel therapeutic target for fear and anxiety disorders.

neuroscience↗