TY - JOUR
T1 - Human stem cell-derived spinal cord astrocytes with defined mature or reactive phenotypes
AU - Roybon, Laurent
AU - Lamas, Nuno J.
AU - Garcia-Diaz, Alejandro
AU - Yang, Eun Ju
AU - Sattler, Rita
AU - Jackson-Lewis, Vernice
AU - Kim, Yoon A.
AU - Kachel, C. Alan
AU - Rothstein, Jeffrey D.
AU - Przedborski, Serge
AU - Wichterle, Hynek
AU - Henderson, Christopher E.
N1 - Funding Information:
We thank M.W. Amoroso and G.F. Croft (Project A.L.S. Laboratory) for sharing data on pilot astrocyte differentiations using noggin, D.H. Oakley for advice on calcium imaging, and B.E. Lewis for help with cell culture and western blotting. H. Hua provided valuable input on qPCR reagents, and the Eggan Laboratory (Harvard Stem Cell Institute) and H. Mitsumoto, J. Montes, P. Kaufmann, and J. Andrews (Columbia) collaborated to generate hiPSCs. We thank J. Goldman for critical reading of the manuscript and N. Maragakis, J. Goldman, M. Rao, B. Barres, members of all our labs and the investigators of the P 2 ALS consortium, as well as Valerie and Meredith Estess for many helpful discussions. This work was funded by Project A.L.S. and P 2 ALS. L.R. was supported by Project A.L.S., the Dr. Leigh G. Cascarilla Post-Doctoral Fellowships in Stem Cell Research, and the Swedish Brain Foundation/Hjärnfonden. N.J.L. was supported by the Portuguese Foundation for Science and Technology SFRH/BD/33421/2008 and the Luso-American Development Foundation. S.P. and V.J.L. were funded through NINDS R01 NS042269-05A2. S.P. is the recipient of the Page and William Black professorship, and C.E.H. is the Gurewitsch/Vidda Professor of Regenerative Medicine.
PY - 2013/5/12
Y1 - 2013/5/12
N2 - Differentiation of astrocytes from human stem cells has significant potential for analysis of their role in normal brain function and disease, but existing protocols generate only immature astrocytes. Using early neuralization, we generated spinal cord astrocytes from mouse or human embryonic or induced pluripotent stem cells with high efficiency. Remarkably, short exposure to fibroblast growth factor 1 (FGF1) or FGF2 was sufficient to direct these astrocytes selectively toward a mature quiescent phenotype, as judged by both marker expression and functional analysis. In contrast, tumor necrosis factor alpha and interleukin-1β, but not FGFs, induced multiple elements of a reactive inflammatory phenotype but did not affect maturation. These phenotypically defined, scalable populations of spinal cord astrocytes will be important both for studying normal astrocyte function and for modeling human pathological processes invitro
AB - Differentiation of astrocytes from human stem cells has significant potential for analysis of their role in normal brain function and disease, but existing protocols generate only immature astrocytes. Using early neuralization, we generated spinal cord astrocytes from mouse or human embryonic or induced pluripotent stem cells with high efficiency. Remarkably, short exposure to fibroblast growth factor 1 (FGF1) or FGF2 was sufficient to direct these astrocytes selectively toward a mature quiescent phenotype, as judged by both marker expression and functional analysis. In contrast, tumor necrosis factor alpha and interleukin-1β, but not FGFs, induced multiple elements of a reactive inflammatory phenotype but did not affect maturation. These phenotypically defined, scalable populations of spinal cord astrocytes will be important both for studying normal astrocyte function and for modeling human pathological processes invitro
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U2 - 10.1016/j.celrep.2013.06.021
DO - 10.1016/j.celrep.2013.06.021
M3 - Article
C2 - 23994478
AN - SCOPUS:84884146442
SN - 2211-1247
VL - 4
SP - 1035
EP - 1048
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -