Discovery of novel cell surface markers for purification of embryonic dopamine progenitors for transplantation in Parkinson's disease animal models

Ali Fathi, Mehdi Mirzaei, Banafsheh Dolatyar, Mehdi Sharifitabar, Mahnaz Bayat, Ebrahim Shahbazi, Jaesuk Lee, Mohammad Javan, Su-Chun Zhang, Vivek Gupta, Bonghee Lee, Paul A. Haynes, Hossein Baharvand, Ghasem Hosseini Salekdeh

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Despite the progress in safety and efficacy of cell replacement therapy with pluripotent stem cells (PSCs), the presence of residual undifferentiated stem cells or proliferating neural progenitor cells with rostral identity remains a major challenge. Here we report the generation of a LIM homeobox transcription factor 1 alpha (LMX1A) knock-in GFP reporter human embryonic stem cell (hESC) line that marks the early dopaminergic progenitors during neural differentiation to find reliable membrane protein markers for isolation of midbrain dopaminergic neurons. Purified GFP positive cells in vitro exhibited expression of mRNA and proteins that characterized and matched the midbrain dopaminergic identity. Further quantitative proteomics analysis of enriched LMX1A+ cells identified several membrane-associated proteins including a polysialylated embryonic form of neural cell adhesion molecule (PSA-NCAM) and contactin 2 (CNTN2), enabling prospective isolation of LMX1A+ progenitor cells. Transplantation of human-PSC-derived purified CNTN2+ progenitors enhanced dopamine release from transplanted cells in the host brain and alleviated Parkinson's disease-related phenotypes in animal models. This study establishes an efficient approach for purification of large numbers of human-PSC-derived dopaminergic progenitors for therapeutic applications.

Original languageEnglish
Pages (from-to)1670-1684
Number of pages15
JournalMolecular and Cellular Proteomics
Volume17
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

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