Browsing by Author "Wan, Yang"

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    Bmi1 promotes erythroid development through regulating ribosome biogenesis
    (Wiley, 2015-03) Gao, Rui; Chen, Sisi; Kobayashi, Michihiro; Yu, Hao; Zhang, Yingchi; Wan, Yang; Young, Sara K.; Soltis, Anthony; Yu, Ming; Vemula, Sasidhar; Fraenkel, Ernest; Cantor, Alan; Antipin, Yevgeniy; Xu, Yang; Yoder, Mervin C.; Wek, Ronald C.; Ellis, Steven R.; Kapur, Reuben; Zhu, Xiaofan; Liu, Yan; Department of Pediatrics, Indiana University School of Medicine
    While Polycomb group protein Bmi1 is important for stem cell maintenance, its role in lineage commitment is largely unknown. We have identified Bmi1 as a novel regulator of erythroid development. Bmi1 is highly expressed in mouse erythroid progenitor cells and its deficiency impairs erythroid differentiation. BMI1 is also important for human erythroid development. Furthermore, we discovered that loss of Bmi1 in erythroid progenitor cells results in decreased transcription of multiple ribosomal protein genes and impaired ribosome biogenesis. Bmi1 deficiency stabilizes p53 protein, leading to upregulation of p21 expression and subsequent G0/G1 cell cycle arrest. Genetic inhibition of p53 activity rescues the erythroid defects seen in the Bmi1 null mice, demonstrating that a p53-dependent mechanism underlies the pathophysiology of the anemia. Mechanistically, Bmi1 is associated with multiple ribosomal protein genes and may positively regulate their expression in erythroid progenitor cells. Thus, Bmi1 promotes erythroid development, at least in part through regulating ribosome biogenesis. Ribosomopathies are human disorders of ribosome dysfunction, including Diamond-Blackfan anemia (DBA) and 5q- syndrome, in which genetic abnormalities cause impaired ribosome biogenesis, resulting in specific clinical phenotypes. We observed that BMI1 expression in human hematopoietic stem and progenitor cells from patients with DBA is correlated with the expression of some ribosomal protein genes, suggesting that BMI1 deficiency may play a pathological role in DBA and other ribosomopathies.
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    Plasma miRNAs across the Alzheimer's disease continuum: Relationship to central biomarkers
    (Wiley, 2024) Liu, Shiwei; Park, Tamina; Krüger, Dennis M.; Pena-Centeno, Tonatiuh; Burkhardt, Susanne; Schutz, Anna-Lena; Huang, Yen-Ning; Rosewood, Thea; Chaudhuri, Soumilee; Cho, MinYoung; Risacher, Shannon L.; Wan, Yang; Shaw, Leslie M.; Sananbenesi, Farahnaz; Brodsky, Alexander S.; Lin, Honghuang; Krunic, Andre; Krzysztof Blusztajn, Jan; Saykin, Andrew J.; Delalle, Ivana; Fischer, Andre; Nho, Kwangsik; Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Introduction: MicroRNAs (miRNAs) play important roles in gene expression regulation and Alzheimer's disease (AD) pathogenesis. Methods: We investigated the association between baseline plasma miRNAs and central AD biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 803): amyloid, tau, and neurodegeneration (A/T/N). Differentially expressed miRNAs and their targets were identified, followed by pathway enrichment analysis. Machine learning approaches were applied to investigate the role of miRNAs as blood biomarkers. Results: We identified nine, two, and eight miRNAs significantly associated with A/T/N positivity, respectively. We identified 271 genes targeted by amyloid-related miRNAs with estrogen signaling receptor-mediated signaling among the enriched pathways. Additionally, 220 genes targeted by neurodegeneration-related miRNAs showed enrichment in pathways including the insulin growth factor 1 pathway. The classification performance of demographic information for A/T/N positivity was increased up to 9% with the inclusion of miRNAs. Discussion: Plasma miRNAs were associated with central A/T/N biomarkers, highlighting their potential as blood biomarkers. Highlights: We performed association analysis of microRNAs (miRNAs) with amyloid/tau/neurodegeneration (A/T/N) biomarker positivity. We identified dysregulated miRNAs for A/T/N biomarker positivity. We identified Alzheimer's disease biomarker-specific/common pathways related to miRNAs. miRNAs improved the classification for A/T/N positivity by up to 9%. Our study highlights the potential of miRNAs as blood biomarkers.
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    The plasma miRNAome in ADNI: Signatures to aid the detection of at-risk individuals
    (Wiley, 2024) Krüger, Dennis M.; Pena-Centeno, Tonatiuh; Liu, Shiwei; Park, Tamina; Kaurani, Lalit; Pradhan, Ranjit; Huang, Yen-Ning; Risacher, Shannon L.; Burkhardt, Susanne; Schütz, Anna-Lena; Wan, Yang; Shaw, Leslie M.; Brodsky, Alexander S.; DeStefano, Anita L.; Lin, Honghuang; Schroeder, Robert; Krunic, Andre; Hempel, Nina; Sananbenesi, Farahnaz; Krzysztof Blusztajn, Jan; Saykin, Andrew J.; Delalle, Ivana; Nho, Kwangsik; Fischer, Andre; Alzheimer's Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of Medicine
    Introduction: MicroRNAs are short non-coding RNAs that control proteostasis at the systems level and are emerging as potential prognostic and diagnostic biomarkers for Alzheimer's disease (AD). Methods: We performed small RNA sequencing on plasma samples from 847 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. Results: We identified microRNA signatures that correlate with AD diagnoses and help predict the conversion from mild cognitive impairment (MCI) to AD. Discussion: Our data demonstrate that plasma microRNA signatures can be used to not only diagnose MCI, but also, critically, predict the conversion from MCI to AD. Moreover, combined with neuropsychological testing, plasma microRNAome evaluation helps predict MCI to AD conversion. These findings are of considerable public interest because they provide a path toward reducing indiscriminate utilization of costly and invasive testing by defining the at-risk segment of the aging population. Highlights: We provide the first analysis of the plasma microRNAome for the ADNI study. The levels of several microRNAs can be used as biomarkers for the prediction of conversion from MCI to AD. Adding the evaluation of plasma microRNA levels to neuropsychological testing in a clinical setting increases the accuracy of MCI to AD conversion prediction.