Biology subjects

Ma, K. Y.

Publications and source records attributed to Ma, K. Y..

3 recordsLinked to original sources

bioRxiv2025

Depot-Specific Roles for C/EBPα in White Adipose Tissue Development and Metabolism

Rates of obesity and its associated metabolic comorbidities continue to rise in the developed world. It is well established that in obesity, the distribution and not just amount of excess white adipose tissue (WAT) correlates with a persons risk for comorbidities such as coronary artery disease and type 2 diabetes. Thus, understanding the specific mechanisms that drive WAT development in specific adipose depots could elucidate novel mechanisms of metabolic disease. SNPs near the gene CEBPA have been associated with multiple cardiometabolic traits by human genome-wide association studies, including waist-to-hip ratio, suggesting that CEBPA regulates WAT distribution. CEBPA encodes a well characterized transcription factor (C/EBP) that is long recognized as a master regulator of adipocyte differentiation, yet depot-specific roles for C/EBP have not been previously described. To further investigate this genetic link, we generated mice with adipocyte-specific Cebpa knockout (Cebpa_ASKO) and found that these mice are almost entirely lacking gonadal WAT (gWAT) despite the inguinal WAT (iWAT) being present in near normal amounts. Despite developing, Cebpa_ASKO iWAT contains fewer and larger adipocytes, and fails to expand when challenged with high fat diet. RNA-seq and functional studies demonstrate evidence of altered lipid metabolism and adipocyte function in Cebpa_ASKO iWAT. Finally, Cebpa_ASKO mice have multiple other metabolic phenotypes, including lipid-laden BAT, increased hepatic triglycerides, and increased plasma cholesterol, all of which worsen with prolonged high fat diet feeding. Taken together, these data highlight depot-specific roles for C/EBP in adipose tissue development, as well as the importance of adipocyte C/EBP in maintaining metabolic homeostasis.

physiology↗

bioRxiv2023

Combined analysis of transposable elements and structural variation in maize genomes reveals genome contraction outpaces expansion

BackgroundStructural differences between genomes are a major source of genetic variation that contributes to phenotypic differences. Transposable elements, mobile genetic sequences capable of increasing their copy number and propagating themselves within genomes, can generate structural variation. However, their repetitive nature makes it difficult to characterize fine-scale differences in their presence at specific positions, limiting our understanding of their impact on genome variation. Domesticated maize is a particularly good system for exploring the impact of transposable element proliferation as over 70% of the genome is annotated as transposable elements. High-quality transposable element annotations were recently generated for de-novo genome assemblies of 26 diverse inbred maize lines. ResultsWe generated base-pair resolved pairwise alignments between the B73 maize reference genome and the remaining 25 inbred maize line assemblies. From this data, we classified transposable elements as either shared or polymorphic in a given pairwise comparison. Our analysis uncovered substantial structural variation between lines, representing both putative insertion and deletion events. Putative insertions in SNP depleted regions, which represent recently diverged identity by state blocks, suggest some TE families may still be active. However, our analysis reveals that, genome-wide, deletions of transposable elements account for more structural variation than insertions. These deletions are often large structural variants containing multiple transposable elements. ConclusionsCombined, our results highlight how transposable elements contribute to structural variation and demonstrate that deletion events are a major contributor to genomic differences.

genomics↗

bioRxiv2018

Fast fluorescence lifetime imaging reveals the maturation process of α-synuclein aggregates in ageing Caenorhabditis elegans

The nematode worm Caenorhabditis elegans has emerged as an important model organism to study the molecular mechanisms of protein misfolding diseases associated with amyloid formation because of its small size, ease of genetic manipulation and optical transparency. Obtaining a reliable and quantitative read-out of protein aggregation in this system, however, remains a challenge. To address this problem, we here present a fast time-gated fluorescence lifetime imaging (TG-FLIM) method and show that it provides functional insights into the process of protein aggregation in living animals by enabling the rapid characterisation of different types of aggregates. More specifically, in longitudinal studies of C. elegans models of Parkinsons and Huntingtons diseases, we observed marked differences in the aggregation kinetics and the nature of the protein inclusions formed by -synuclein and polyglutamine. In particular, we found that -synuclein inclusions do not display amyloid-like features until late in the life of the worms, whereas polyglutamine forms amyloid characteristics rapidly in early adulthood. Furthermore, we show that the TG-FLIM method is capable of imaging live and non-anaesthetised worms moving in specially designed agarose micro-chambers. Taken together, our results show that the TG-FLIM method enables high-throughput functional imaging of living C. elegans that can be used to study in vivo mechanisms of aggregation and that has the potential to aid the search for therapeutic modifiers of protein aggregation and toxicity.

biophysics↗