Transcriptome analysis reveals transmembrane targets on transplantable midbrain dopamine progenitors

Proceedings of the National Academy of Sciences of the United States of America
Chris R ByeLachlan H Thompson

Abstract

An important challenge for the continued development of cell therapy for Parkinson's disease (PD) is the establishment of procedures that better standardize cell preparations for use in transplantation. Although cell sorting has been an anticipated strategy, its application has been limited by lack of knowledge regarding transmembrane proteins that can be used to target and isolate progenitors for midbrain dopamine (mDA) neurons. We used a "FACS-array" approach to identify 18 genes for transmembrane proteins with high expression in mDA progenitors and describe the utility of four of these targets (Alcam, Chl1, Gfra1, and Igsf8) for isolating mDA progenitors from rat primary ventral mesencephalon through flow cytometry. Alcam and Chl1 facilitated a significant enrichment of mDA neurons following transplantation, while targeting of Gfra1 allowed for robust separation of dopamine and serotonin neurons. Importantly, we also show that mDA progenitors isolated on the basis of transmembrane proteins are capable of extensive, functional innervation of the host striatum and correction of motor impairment in a unilateral model of PD. These results are highly relevant for current efforts to establish safe and effective stem cell-based pro...Continue Reading

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Citations

Sep 30, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Olle Lindvall
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ole Isacson
Feb 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Agnieszka KotarskaMelitta Schachner
Jan 14, 2020·The Journal of Clinical Investigation·Jun Takahashi
Dec 7, 2018·International Journal of Molecular Sciences·Takayasu MishimaYoshio Tsuboi
Sep 10, 2020·Frontiers in Cell and Developmental Biology·Tae Wan KimLorenz Studer
Aug 1, 2020·Frontiers in Cell and Developmental Biology·Emilía Sif Ásgrímsdóttir, Ernest Arenas
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Jul 28, 2020·Cellular and Molecular Life Sciences : CMLS·Anna MeyfourGhasem Hosseini Salekdeh
Jan 26, 2021·Regenerative Therapy·Jun Takahashi

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