<p>Cell surface markers are important tools for quality control (QC) and enrichment of cellular subtypes, such as the dopaminergic (DA) progenitors used for treatment of Parkinson’s disease (PD). However, the regional specificity of many published surface markers is not fully known. Here, we identified APCDD1 as a surface marker with high regional selectivity for caudal ventral midbrain DA fate, outperforming the specificity of seven other previously published markers in flow cytometry analysis. APCDD1 expression correlated with key markers of caudal ventral midbrain DA fate, and antibody-based sorting for APCDD1 enabled enrichment of DA progenitors and depletion of non-DA populations. In regionally mixed neural populations, APCDD1-high, but not APCDD1-low cells, yielded full motoric amelioration after grafting in a rat model of PD, and the APCDD1-high cells produced a higher proportion of DA neurons co-expressing ventral midbrain markers FOXA2 and LMX1A. Taken together, APCDD1 is a promising tool for improving the QC and enrichment of clinically applied cell products for PD.</p>

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APCDD1 shows high specificity for ventral midbrain dopaminergic progenitors in a cell surface marker benchmarking study

  • Alrik L. Schörling,
  • Alison Salvador,
  • Pedro Rifes,
  • Erno Hänninen,
  • Amalie Holm Nygaard,
  • Gaurav Singh Rathore,
  • Jenny Nelander,
  • Josefine Rågård Christiansen,
  • Simone Møller Jensen,
  • Jonathan Christos Niclis,
  • Emma Gustafsson,
  • Patrick Aldrin-Kirk,
  • Yu Zhang,
  • Malin Parmar,
  • Agnete Kirkeby

摘要

Cell surface markers are important tools for quality control (QC) and enrichment of cellular subtypes, such as the dopaminergic (DA) progenitors used for treatment of Parkinson’s disease (PD). However, the regional specificity of many published surface markers is not fully known. Here, we identified APCDD1 as a surface marker with high regional selectivity for caudal ventral midbrain DA fate, outperforming the specificity of seven other previously published markers in flow cytometry analysis. APCDD1 expression correlated with key markers of caudal ventral midbrain DA fate, and antibody-based sorting for APCDD1 enabled enrichment of DA progenitors and depletion of non-DA populations. In regionally mixed neural populations, APCDD1-high, but not APCDD1-low cells, yielded full motoric amelioration after grafting in a rat model of PD, and the APCDD1-high cells produced a higher proportion of DA neurons co-expressing ventral midbrain markers FOXA2 and LMX1A. Taken together, APCDD1 is a promising tool for improving the QC and enrichment of clinically applied cell products for PD.