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Öğe In vitro myelin formation using embryonic stem cells(Company of Biologists, 2015) Kerman, Bilal Ersen; Kim, Hyung-joon; Padmanabhan, Krishnan; Mei, Arianna; Georges, Shereen; Joens, Matthew; Fitzpatrick, James; Jappelli, Roberto; Chandross, Karen; August, Paul; Gage, FredMyelination in the central nervous system is the process by which oligodendrocytes form myelin sheaths around the axons of neurons. Myelination enables neurons to transmit information more quickly and more efficiently and allows for more complex brain functions; yet, remarkably, the underlying mechanism by which myelination occurs is still not fully understood. A reliable in vitro assay is essential to dissect oligodendrocyte and myelin biology. Hence, we developed a protocol to generate myelinating oligodendrocytes from mouse embryonic stem cells and established a myelin formation assay with embryonic stem cell-derived neurons in microfluidic devices. Myelin formation was quantified using a custom semi-automated method that is suitable for larger scale analysis. Finally, early myelination was followed in real time over several days and the results have led us to propose a new model for myelin formation.Öğe Species-specific maturation profiles of human, chimpanzee and bonobo neural cells(Elife Sciences Publications Ltd, 2019) Marchetto, Maria Carolina; Hrvoj-Mihic, Branka; Kerman, Bilal Ersen; Yu, Diana X.; Vadodaria, Krishna C.; Linker, Sara B.; Narvaiza, Inigo; Santos, Renata; Denli, Ahmet M.; Mendes, Ana P. D.; Oefner, Ruth; Cook, Jonathan; McHenry, Lauren; Grasmick, Jaeson M.; Heard, Kelly; Fredlender, Callie; Randolph-Moore, Lynne; Kshirsagar, Rijul; Xenitopoulos, Rea; Chou, Grace; Hah, Nasun; Muotri, Alysson R.; Padmanabhan, Krishnan; Semendeferi, Katerina; Gage, Fred H.Comparative analyses of neuronal phenotypes in closely related species can shed light on neuronal changes occurring during evolution. The study of post-mortem brains of nonhuman primates (NHPs) has been limited and often does not recapitulate important species-specific developmental hallmarks. We utilize induced pluripotent stem cell (iPSC) technology to investigate the development of cortical pyramidal neurons following migration and maturation of cells grafted in the developing mouse cortex. Our results show differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos both in vitro and in vivo, suggesting heterochronic changes in human neurons. The strategy proposed here lays the groundwork for further comparative analyses between humans and NHPs and opens new avenues for understanding the differences in the neural underpinnings of cognition and neurological disease susceptibility between species.











