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
AU - Elefanty, Andrew George
AU - Sasai, Yoshiki
AU - Alvarez-Buylla, Arturo
AU - Rubenstein, John L R
AU - Kriegstein, Arnold R
PY - 2013
Y1 - 2013
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.ncbi.nlm.nih.gov/pubmed/23642366
U2 - 10.1016/j.stem.2013.04.005
DO - 10.1016/j.stem.2013.04.005
M3 - Article
VL - 12
SP - 573
EP - 586
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 5
ER -