@article{9e3caffc23e34f829b4390fd285e11a0,
title = "Role of astroglia in down's syndrome revealed by patient-derived human-induced pluripotent stem cells",
abstract = "Down's syndrome (DS), caused by trisomy of human chromosome 21, is the most common genetic cause of intellectual disability. Here we use induced pluripotent stem cells (iPSCs) derived from DS patients to identify a role for astrocytes in DS pathogenesis. DS astroglia exhibit higher levels of reactive oxygen species and lower levels of synaptogenic molecules. Astrocyte-conditioned medium collected from DS astroglia causes toxicity to neurons, and fails to promote neuronal ion channel maturation and synapse formation. Transplantation studies show that DS astroglia do not promote neurogenesis of endogenous neural stem cells in vivo. We also observed abnormal gene expression profiles from DS astroglia. Finally, we show that the FDA-approved antibiotic drug, minocycline, partially corrects the pathological phenotypes of DS astroglia by specifically modulating the expression of S100B, GFAP, inducible nitric oxide synthase, and thrombospondins 1 and 2 in DS astroglia. Our studies shed light on the pathogenesis and possible treatment of DS by targeting astrocytes with a clinically available drug.",
author = "Chen Chen and Peng Jiang and Haipeng Xue and Peterson, {Suzanne E.} and Tran, {Ha T.} and McCann, {Anna E.} and Parast, {Mana M.} and Shenglan Li and Pleasure, {David E.} and Laurent, {Louise C.} and Loring, {Jeanne F.} and Ying Liu and Wenbin Deng",
note = "Funding Information: We thank Dr Fuzheng Guo at University of California, Davis for technical assistance. This work was in part supported by grants from National Institutes of Health (R01NS061983 and R01ES015988, to W.D.), the National Multiple Sclerosis Society (to W.D.) and Shriners Hospitals for Children (to W.D.). Y.L. was supported by California Institute of Regenerative Medicine (RT1-011071), the Memorial Hermann Foundation (Staman Ogilvie Fund) and the Bentsen Stroke Center. C.C. is supported by a postdoctoral fellowship from California Institute of Regenerative Medicine. P.J. is a recipient of a postdoctoral fellowship from Shriners Hospitals for Children. S.E.P., H.T.T. and J.F.L. were supported by California Institute for Regenerative Medicine (RT1-01108, TR1-01250 and CL1-00502), NIH (R21 MH087925) and the Esther O{\textquoteright}Keeffe Foundation. A.E.M. was supported by a California Institute for Regenerative Medicine Bridges to Stem Cell Research Internship. L.C.L. was supported by NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Career Development Award (K12 HD001259) and the Hartwell Foundation.",
year = "2014",
month = jul,
day = "18",
doi = "10.1038/ncomms5430",
language = "English (US)",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}