Cortical Neurons Derived from Equine Induced Pluripotent Stem Cells Are Susceptible to Neurotropic Flavivirus Infection and Replication: An In Vitro Model for Equine Neuropathic Diseases

2018 ◽  
Vol 27 (10) ◽  
pp. 704-715 ◽  
Author(s):  
Patrick R.J. Fortuna ◽  
Helle Bielefeldt-Ohmann ◽  
Dmitry A. Ovchinnikov ◽  
Ernst J. Wolvetang ◽  
Deanne J. Whitworth
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cortical Neurons ◽  
In Vitro Model ◽  
Vitro Model ◽  
Induced Pluripotent ◽  
Flavivirus Infection

scholarly journals Modeling congenital cataract in vitro using patient-specific induced pluripotent stem cells

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Danni Lyu ◽  
Lifang Zhang ◽  
Zhenwei Qin ◽  
Shuang Ni ◽  
Jiayong Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Congenital Cataract ◽  
In Vitro Model ◽  
Patient Specific ◽  
Congenital Cataracts ◽  
Vitro Model ◽  
Induced Pluripotent

AbstractCongenital cataracts are the leading cause of childhood blindness. To date, surgical removal of cataracts is the only established treatment, but surgery is associated with multiple complications, which often lead to visual impairment. Therefore, mechanistic studies and drug-candidate screening have been intrigued by the aims of developing novel therapeutic strategies. However, these studies have been hampered by a lack of an appropriate human-disease model of congenital cataracts. Herein, we report the establishment of a human congenital cataract in vitro model through differentiation of patient-specific induced pluripotent stem cells (iPSCs) into regenerated lenses. The regenerated lenses derived from patient-specific iPSCs with known causative mutations of congenital cataracts (CRYBB2 [p. P24T] and CRYGD [p. Q155X]) showed obvious opacification that closely resembled that seen in patients’ cataracts in terms of opacification severity and disease course accordingly, as compared with lentoid bodies (LBs) derived from healthy individuals. Increased protein aggregation and decreased protein solubility corresponding to the patients’ cataract severity were observed in the patient-specific LBs and were attenuated by lanosterol treatment. Taken together, the in vitro model described herein, which recapitulates patient-specific clinical manifestations of congenital cataracts and protein aggregation in patient-specific LBs, provides a robust system for research on the pathological mechanisms of cataracts and screening of drug candidates for cataract treatment.

scholarly journals In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kento Nakai ◽  
Takahiro Shiga ◽  
Rika Yasuhara ◽  
Avijite Kumer Sarkar ◽  
Yuka Abe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neurological Diseases ◽  
Electrophysiological Properties ◽  
Maturation Stages ◽  
Vitro Model ◽  
Induced Pluripotent

AbstractThe serotonin 5-HT2A receptor (5-HT2AR) has been receiving increasing attention because its genetic variants have been associated with a variety of neurological diseases. To elucidate the pathogenesis of the neurological diseases associated with 5-HT2AR gene (HTR2A) variants, we have previously established a protocol to induce HTR2A-expressing neurons from human-induced pluripotent stem cells (hiPSCs). Here, we investigated the maturation stages and electrophysiological properties of HTR2A-positive neurons induced from hiPSCs and constructed an HTR2A promoter-specific reporter lentivirus to label the neurons. We found that neuronal maturity increased over time and that HTR2A expression was induced at the late stage of neuronal maturation. Furthermore, we demonstrated successful labelling of the HTR2A-positive neurons, which had fluorescence and generated repetitive action potentials in response to depolarizing currents and an inward current during the application of TCB-2, a selective agonist of 5-HT2ARs, respectively. These results indicated that our in vitro model mimicked the in vivo dynamics of 5-HT2AR. Therefore, in vitro monitoring of the function of HTR2A-positive neurons induced from hiPSCs could help elucidate the pathophysiological mechanisms of neurological diseases associated with genetic variations of the HTR2A gene.

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