Browsing by Subject "Induced pluripotent 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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    Genetic resiliency associated with dominant lethal TPM1 mutation causing atrial septal defect with high heritability
    (Elsevier, 2022-02-15) Teekakirikul, Polakit; Zhu, Wenjuan; Xu, Xinxiu; Young, Cullen B.; Tan, Tuantuan; Smith, Amanda M.; Wang, Chengdong; Peterson, Kevin A.; Gabriel, George C.; Ho, Sebastian; Sheng, Yi; de Bellaing, Anne Moreau; Sonnenberg, Daniel A.; Lin, Jiuann-huey; Fotiou, Elisavet; Tenin, Gennadiy; Wang, Michael X.; Wu, Yijen L.; Feinstein, Timothy; Devine, William; Gou, Honglan; Bais, Abha S.; Glennon, Benjamin J.; Zahid, Maliha; Wong, Timothy C.; Ahmad, Ferhaan; Rynkiewicz, Michael J.; Lehman, William J.; Keavney, Bernard; Alastalo, Tero-Pekka; Freckmann, Mary-Louise; Orwig, Kyle; Murray, Steve; Ware, Stephanie M.; Zhao, Hui; Feingold, Brian; Lo, Cecilia W.; Pediatrics, School of Medicine
    Analysis of large-scale human genomic data has yielded unexplained mutations known to cause severe disease in healthy individuals. Here, we report the unexpected recovery of a rare dominant lethal mutation in TPM1, a sarcomeric actin-binding protein, in eight individuals with large atrial septal defect (ASD) in a five-generation pedigree. Mice with Tpm1 mutation exhibit early embryonic lethality with disrupted myofibril assembly and no heartbeat. However, patient-induced pluripotent-stem-cell-derived cardiomyocytes show normal beating with mild myofilament defect, indicating disease suppression. A variant in TLN2, another myofilament actin-binding protein, is identified as a candidate suppressor. Mouse CRISPR knock-in (KI) of both the TLN2 and TPM1 variants rescues heart beating, with near-term fetuses exhibiting large ASD. Thus, the role of TPM1 in ASD pathogenesis unfolds with suppression of its embryonic lethality by protective TLN2 variant. These findings provide evidence that genetic resiliency can arise with genetic suppression of a deleterious mutation.
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    Robust Differentiation of mRNA-Reprogrammed Human Induced Pluripotent Stem Cells Toward a Retinal Lineage.
    (AlphaMed Press, 2016-04) Sridhar, Akshayalakshmi; Ohlemacher, Sarah K.; Langer, Kirstin B.; Meyer, Jason S.; Department of Biology, School of Science
    The ability and efficiency of mRNA-reprogrammed human induced pluripotent stem cells (hiPSCs) to yield retinal cell types in a directed, stepwise manner was tested. hiPSCs derived through mRNA-based reprogramming strategies offer numerous advantages owing to the lack of genomic integration or constitutive expression of pluripotency genes. Such methods represent a promising new approach for retinal stem cell research, especially translational applications.