Activin A directs striatal projection neuron differentiation of human pluripotent stem cells
The Company of Biologists
MetadataShow full item record
The efficient generation of striatal neurons from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) is fundamental for realising their promise in disease modelling, pharmaceutical drug screening and cell therapy for Huntington's disease. GABAergic medium-sized spiny neurons (MSNs) are the principal projection neurons of the striatum and specifically degenerate in the early phase of Huntington's disease. Here we report that activin A induces lateral ganglionic eminence (LGE) characteristics in nascent neural progenitors derived from hESCs and hiPSCs in a sonic hedgehog-independent manner. Correct specification of striatal phenotype was further demonstrated by the induction of the striatal transcription factors CTIP2, GSX2 and FOXP2. Crucially, these human LGE progenitors readily differentiate into postmitotic neurons expressing the striatal projection neuron signature marker DARPP32, both in culture and following transplantation in the adult striatum in a rat model of Huntington's disease. Activin-induced neurons also exhibit appropriate striatal-like electrophysiology in vitro. Together, our findings demonstrate a novel route for efficient differentiation of GABAergic striatal MSNs from human pluripotent stem cells
Aber, C., Precious, S. V., Cambray, S., Risner-Janiczek, J.R., Kelly, C., Noakes, Z., Fjodorova, M., Heuer, A., Ungless, M.A., Rodriguez, T.A., Rosser, A.E., Dunnett, S.B. and Li, M. (2015) 'Activin A directs striatal projection neuron differentiation of human pluripotent stem cells', Development, 142 (7), pp.1375-1386.
This article was published in Development on 1st April 2015 (online), available at http://dev.biologists.org/content/142/7/1375
RightsCreative Commons (CC-BY 3.0) license
Except where otherwise noted, this item's license is described as Creative Commons (CC-BY 3.0) license
Showing items related by title, author, subject and abstract.
FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation Precious, S.V.; Kelly, Claire; Reddington, A.E.; Vinh, N.N.; Stickland, R.C.; Pekarik, V.; Scherf, C.; Jeyasingham, R.; Glasbey, J.; Holeiter, M.; Jones, L.; Taylor, M.V.; Rosser, A.E. (Elsevier, 2016-08)Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The ...
Human Pluripotent Stem Cell-Derived Striatal Interneurons: Differentiation and Maturation In Vitro and in the Rat Brain Noakes, Zoe; Keefe, Francesca; Tamburini, Claudia; Kelly, Claire; Maria, Cruz Santos; Dunnett, Stephen; Errington, Adam; Meng, Li (Elsevier, 2019-01-17)Striatal interneurons are born in the medial and caudal ganglionic eminences (MGE and CGE) and play an important role in human striatal function and dysfunction in Huntington’s disease and dystonia. MGE/CGE-like neural ...
Can manipulation of differentiation conditions eliminate proliferative cells from a population of ES cell-derived forebrain cells? Precious, Sophie V.; Kelly, Claire; Allen, Nicholas D.; Rosser, Anne E. (Taylor Francis, 2016-01-11)There is preliminary evidence that implantation of primary fetal striatal cells provides functional benefit in patients with Huntington’s disease, a neurodegenerative condition resulting in loss of medium-sized spiny neurons ...