TY - JOUR
T1 - Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development
AU - Nicholas, Cory R.
AU - Chen, Jiadong
AU - Tang, Yunshuo
AU - Southwell, Derek G.
AU - Chalmers, Nadine
AU - Vogt, Daniel
AU - Arnold, Christine M.
AU - Chen, Ying Jiun J.
AU - Stanley, Edouard G.
AU - Elefanty, Andrew G.
AU - Sasai, Yoshiki
AU - Alvarez-Buylla, Arturo
AU - Rubenstein, John L.R.
AU - Kriegstein, Arnold R.
N1 - Funding Information:
We thank S. Baraban, R. Hunt, D. Wang, S. Gee, P. Parker, and M. Yang for electrophysiology guidance and discussion. We thank D. Hansen, J. Lui, M. Oldham, M. Paredes, C. Harwell, X. Wang, S. Wang, Y. Wang, S. Hart, R. Romero, T. Nguyen, and W. Walantus for helpful discussion, gene expression, cell culture, tissue procurement, processing, and technical assistance. We thank K. Probst for graphical design. We thank M. Ramalho-Santos and Y. Ohi for hiPSC lines, K. Deisseroth for the ChR2-EYFP plasmid, and K. Yoshikawa for the DLX2 antibody. We thank the staff and faculty at the San Francisco General Hospital Women’s Options Center and at Advanced Bioscience Resources who assisted in human fetal tissue collection. This work was supported by the California Institute of Regenerative Medicine (RC1-00346 to A.R.K., RB2-01602 to J.L.R.R., and TR2-01749 to A.A.-B.), the National Institute of Neurological Disorders and Stroke, and the Osher Foundation. J.C. is a recipient of the CARE & CURE Pediatric Epilepsy Fellowship from Epilepsy Foundation of Greater Los Angeles. A.G.E. and E.G.S. are Senior Research Fellows of the National Health and Medical Research Council of Australia. C.R.N., A.A.-B., J.L.R.R., and A.R.K. are cofounders, board members, and shareholders of Neurona Therapeutics.
PY - 2013/5/2
Y1 - 2013/5/2
N2 - Directed differentiation from human pluripotent stem cells (hPSCs) has seen significant progress in recent years. However, most differentiated populations exhibit immature properties of an early embryonic stage, raising concerns about their ability to model and treat disease. Here, we report the directed differentiation of hPSCs into medial ganglionic eminence (MGE)-like progenitors and their maturation into forebrain type interneurons. We find that early-stage progenitors progress via a radial glial-like stem cell enriched in the human fetal brain. Both in vitro and posttransplantation into the rodent cortex, the MGE-like cells develop into GABAergic interneuron subtypes with mature physiological properties along a prolonged intrinsic timeline of up to 7 months, mimicking endogenous human neural development. MGE-derived cortical interneuron deficiencies are implicated in a broad range of neurodevelopmental and degenerative disorders, highlighting the importance of these results for modeling human neural development and disease.
AB - Directed differentiation from human pluripotent stem cells (hPSCs) has seen significant progress in recent years. However, most differentiated populations exhibit immature properties of an early embryonic stage, raising concerns about their ability to model and treat disease. Here, we report the directed differentiation of hPSCs into medial ganglionic eminence (MGE)-like progenitors and their maturation into forebrain type interneurons. We find that early-stage progenitors progress via a radial glial-like stem cell enriched in the human fetal brain. Both in vitro and posttransplantation into the rodent cortex, the MGE-like cells develop into GABAergic interneuron subtypes with mature physiological properties along a prolonged intrinsic timeline of up to 7 months, mimicking endogenous human neural development. MGE-derived cortical interneuron deficiencies are implicated in a broad range of neurodevelopmental and degenerative disorders, highlighting the importance of these results for modeling human neural development and disease.
UR - http://www.scopus.com/inward/record.url?scp=84877301288&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2013.04.005
DO - 10.1016/j.stem.2013.04.005
M3 - Article
C2 - 23642366
AN - SCOPUS:84877301288
SN - 1934-5909
VL - 12
SP - 573
EP - 586
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 5
ER -