APCDD1 outperforms other dopaminergic cell surface markers in benchmarking study

Abstract

Cell surface markers are useful tools for quality control and enrichment of cellular subtypes, such as the dopaminergic progenitors used in the treatment of Parkinson’s disease (PD). Here, we identified a candidate dopaminergic (DA) progenitor surface marker, APCDD1, and benchmarked its specificity against 7 other previously published markers. APCDD1 correlated with key markers of ventral midbrain DA fate and outperformed the 7 other markers in specificity. Antibody-based sorting for APCDD1 enabled enrichment of DA progenitors and depletion of neighbouring non-DA populations. When sorting from mixed cell populations, only APCDD1+ cells, and not APCDD1- cells, yielded full motoric amelioration after grafting in a rat model of PD, and the APCDD1+ grafts contained a higher proportion of DA neurons co-expressing ventral midbrain markers FOXA2 and LMX1A. Taken together, APCDD1 outperformed previously published surface markers and will be useful for improving the quality control and enrichment of clinically applied cell products for PD.