Browsing by Subject "Embryonic stem cell"

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    A brief review of recent advances in stem cell biology
    (Wolters Kluwer, 2014) Chen, Jinhui; Zhou, Libing; Pan, Su-yue; Neurological Surgery, School of Medicine
    Stem cells have the remarkable potential to develop into many different cell types, essentially without limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer's disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. Recent breakthrough make it possible to convert or "reprogram" specialized adult cells to assume a stem stem-like cells with different technologies. The review will briefly discuss the recent progresses in this area.
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    Defective Tmprss3-Associated Hair Cell Degeneration in Inner Ear Organoids
    (Elsevier, 2019-07-09) Tang, Pei-Ciao; Alex, Alpha L.; Nie, Jing; Lee, Jiyoon; Roth, Adam A.; Booth, Kevin T.; Koehler, Karl R.; Hashino, Eri; Nelson, Rick F.; Otolaryngology, IU School of Medicine
    Mutations in the gene encoding the type II transmembrane protease 3 (TMPRSS3) cause human hearing loss, although the underlying mechanisms that result in TMPRSS3-related hearing loss are still unclear. We combined the use of stem cell-derived inner ear organoids with single-cell RNA sequencing to investigate the role of TMPRSS3. Defective Tmprss3 leads to hair cell apoptosis without altering the development of hair cells and the formation of the mechanotransduction apparatus. Prior to degeneration, Tmprss3-KO hair cells demonstrate reduced numbers of BK channels and lower expressions of genes encoding calcium ion-binding proteins, suggesting a disruption in intracellular homeostasis. A proteolytically active TMPRSS3 was detected on cell membranes in addition to ER of cells in inner ear organoids. Our in vitro model recapitulated salient features of genetically associated inner ear abnormalities and will serve as a powerful tool for studying inner ear disorders.
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    Mediator and SAGA Have Distinct Roles in Pol II Preinitiation Complex Assembly and Function
    (Elsevier, 2012) Chen, Xiao-Fen; Lehmann, Lynn; Lin, Justin J.; Vashisht, Ajay; Schmidt, Ryan; Ferrari, Roberto; Huang, Chengyang; McKee, Robin; Mosley, Amber; Plath, Kathrin; Kurdistani, Siavash K.; Wohlschlegel, James; Carey, Michael; Biochemistry and Molecular Biology, School of Medicine
    A key feature of RNA polymerase II preinitiation complexes (PICs) is their ability to coordinate transcription initiation with chromatin modification and remodeling. To understand how this coordination is achieved, we employed extensive proteomic and mechanistic analyses to study the composition and assembly of PICs in HeLa and mouse embryonic stem (ES) cell nuclear extracts. Strikingly, most of the machinery necessary for transcription initiation on chromatin is part of the PIC. The PIC is nearly identical between ES and HeLa cells, and contains two major co-activator complexes, Mediator and SAGA. Genomewide analysis of Mediator reveals a close correlation with Pol II, TBP and mRNA levels implying a major role in PIC assembly. Moreover, Mediator coordinates assembly of the Pol II initiation factors and chromatin machinery into a PIC in vitro, while SAGA acts after PIC assembly to allow transcription on chromatin.