Biology subjects

Chien, C.-C.

Publications and source records attributed to Chien, C.-C..

5 recordsLinked to original sources

bioRxiv2025

The demographic history, genomic variation, and transcontinental genotype-phenotype-environment map of mungbean

The breeding of mungbean, a crucial Asian legume, has been hampered by the lack of genomic resources. The International Mungbean Improvement Network (IMIN) aims to ensure global access to diverse germplasms and genomic resources. Using 780 worldwide wild and cultivated accessions, we report this species most comprehensive (pan)genomic variation, demographic history, and genotype-phenotype-environment map. Despite archaeological evidence of the earliest cultivation in South Asia, present-day wild populations only possess relict traces of shared polymorphisms with cultivars. We showed that parallel losses of black seed coats in two Vigna species were caused by the same mutational mechanism in the same gene. In large-scale cross-continent field trials, we found accessions from distant environments from the trial sites have lower performance, especially in high-heritability and high-yield sites, suggesting future breeding priority in benign conditions on accessions from similar environments. Our comprehensive genomic and trial resources facilitate future breeding success of this essential crop.

evolutionary biology↗

bioRxiv2024

The Taiwan Precision Medicine Initiative: A Cohort for Large-Scale Studies

The Taiwan Precision Medicine Initiative (TPMI), a project initiated by the Academia Sinica in collaboration with 16 major medical centers around Taiwan, has recruited 565,390 participants who consented to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMR) for studies to develop precision medicine. Access to the EMR is both retrospective and prospective, allowing researchers to conduct prospective studies over time. Genetic profiling is done with population-optimized SNP arrays for the Han Chinese populations that enable genetic analyses such as genome-wide association, phenome-wide association, and polygenic risk score studies to evaluate common disease risk and pharmacogenetic response. Furthermore, the TPMI participants agree to be contacted for future research opportunities related to their genetic risks and receive personalized genetic risk profiles with health management recommendations. TPMI has established the TPMI Data Access Platform (TDAP), a central database and analysis platform that both safeguards the security of the data and facilitates academic research. The TPMI is the largest non-European cohort that merges genetic profiles with EMR in the world. With a cohort that can be followed over time, it can be utilized to validate genetic risk prediction models, conduct clinical trials to show the efficacy of risk-based health management, and optimize health policies based on genetic risks. In this report, we describe the TPMI study design, the population and genetic characteristics of the TPMI cohort, and the power it provides to conduct crucial studies in developing precision medicine on a population and personal level. As Han Chinese represent almost 20% of the worlds population, the results of TPMI studies will benefit >1.4 billion people around the world and serve as a model for developing population-based precision medicine.

genetics↗

bioRxiv2024

How weedy Arabidopsis thaliana dominated the world: ancestral variation and polygenic adaptation

The composition of a species could change with demographic turnovers, where dominant populations quickly expanded and replaced others. However, whether such events have a genetic basis remains to be investigated. Previous studies showed that Arabidopsis thaliana experienced a significant demographic turnover, where "non-relicts" replaced "relicts" throughout Eurasia. Here, we showed that non-relicts have smaller seeds, more seeds per fruit, and a higher germination rate, making them more competitive over relicts. Using a unique population enriching relict alleles while minimizing population structure, we identified candidate loci and showed that such trait divergence was caused by the divergent sorting of multiple ancient haplotypes in a Mendelian gene and joint allele frequency change of polygenes affecting single-trait divergence and multi-trait covariance. This study is one of the few genetic investigations of species-wide demographic turnover, emphasizing the importance of processes different from the much-focused hard selective sweep.

evolutionary biology↗

bioRxiv2023

Hydrogen Sulfide Coordinates Glucose Metabolism Switch through Destabilizing Tetrameric Pyruvate Kinase M2

Cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation toward aerobic glycolysis. Pyruvate kinase M2 (PKM2), which converts phosphoenolpyruvate (PEP) to pyruvate, is considered the rate-limiting enzyme involved in cancer glucose metabolism. By reducing PKM2 enzyme activity, cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes PKM2 tetramer into dimer/monomer, leading to reduced PKM2 enzyme activity and an increase in the activation of nuclear transcriptional genes mediated by dimeric PKM2. Proteomic profiling of endogenous PKM2 reveals the occurrence of sulfhydration at cysteines, notably at cysteine 326. Blocking PKM2 sulfhydration at cysteine 326 through amino acid mutation stabilizes PKM2 tetramer and crystal structure further indicating that the tetramer organization of PKM2C326S is different from the currently known T or R states, revealing PKM2C326S as a newly identified form. The presence of a PKM2C326S mutant in cancer cells effectively rewires glucose metabolism to mitochondrial respiration, resulting in the significant inhibition of tumor growth. Collectively, PKM2 sulfhydration by H2S serves as a glucose metabolic rewiring mechanism in promoting tumorigenesis, and inhibition of PKM2 sulfhydration may be applied as a new therapeutic approach targeting cancer metabolism. One-Sentence SummaryH2S rewires glucose metabolism by destabilizing PKM2 tetramerization majorly through sulfhydration at cysteine 326 HighlightsO_LIH2S enhances PKM2 dissociation from tetramer to dimer to facilitate dimeric PKM2 nuclear translocation. C_LIO_LIH2S modifies PKM2 sulfhydration, notably at cysteine 326. C_LIO_LIThe crystal structure reveals PKM2C326S as a unique tetramer conformation. C_LIO_LIBlockage of PKM2 sulfhydration at C326 rewires cancer glucose metabolism and significantly inhibits tumor growth. C_LI

cancer biology↗

bioRxiv2021

Optical Cellular Micromotion: A New Paradigm to Measure Tumour Cells Invasion in 3D Tumour Environments

Measuring tumour cell invasiveness through three-dimensional (3D) tissues, particularly at the single cell level, can provide important mechanistic understanding and assist in identifying therapeutic targets of tumour invasion. However, current experimental approaches, including standard in vitro invasion assays, have limited physiological relevance and offer insufficient insight about the vast heterogeneity in tumour cell migration through tissues. To address these issues, here we report on the concept of optical cellular micromotion, where digital holographic microscopy (DHM) is used to map the optical thickness fluctuations at sub-micron scale within single cells. These fluctuations are driven by the dynamic movement of subcellular structures including the cytoskeleton and inherently associated with the biological processes involved in cell invasion within tissues. We experimentally demonstrate that the optical cellular micromotion correlates with tumour cells motility and invasiveness both at the population and single cell levels. In addition, the optical cellular micromotion significantly reduced upon treatment with migrastatic drugs that inhibit tumour cell invasion. These results demonstrate that micromotion measurements can rapidly and non-invasively determine the invasive behaviour of single tumour cells within tissues, yielding a new and powerful tool to assess the efficacy of approaches targeting tumour cell invasiveness. Significance StatementTumour cells invasion through tissues is a key hallmark of malignant tumour progression and its measurement is essential to unraveling biological processes and screening for new approaches targeting cell motility. To address the limitations of current approaches, we demonstrate that sub-micron scale mapping of the dynamic optical thickness fluctuations within single cells, referred to as optical cellular micromotion, correlates with their motility in ECM mimicking gel, both at the population and single cell levels. We anticipate that 3D optical micromotion measurement will provide a powerful new tool to address important biological questions and screen for new approaches targeting tumour cell invasiveness.

bioengineering↗