Yazar "Randolph-Moore, Lynne" seçeneğine göre listele

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    Differentiation of inflammation-responsive astrocytes from glial progenitors generated from human induced pluripotent stem cells
    (Cell Press, 2017) Santos, Renata; Vadodaria, Krishna C.; Jaeger, Baptiste N.; Mei, Arianna; Lefcochilos-Fogelquist, Sabrina; Mendes, Ana P. D.; Erikson, Galina; Shokhirev, Maxim; Randolph-Moore, Lynne; Fredlender, Callie; Dave, Sonia; Oefner, Ruth; Fitzpatrick, Conor; Pena, Monique; Barron, Jerika J.; Ku, Manching; Denli, Ahmet M.; Kerman, Bilal Ersen; Charnay, Patrick; Kelsoe, John R.; Marchetto, Maria C.; Gage, Fred H.
    Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1 beta or tumor necrosis factor a elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1 beta. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration.
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    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.