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However, the classical differentiation protocols for both mouse and human pluripotent stem cells generate a limited percentage of dopaminergic neurons and yield a considerable cellular heterogeneity comprising numerous scarcely characterized cell populations. To improve pluripotent stem cell differentiation protocols for midbrain dopaminergic neurons, we established extensive and strictly quantitative gene expression profiles, including markers for pluripotent cells, neural progenitors, non-neural cells, pan-neuronal and glial cells, neurotransmitter phenotypes, midbrain and nonmidbrain populations, floor plate and basal plate populations, as well as for Hedgehog, Fgf, and Wnt signaling pathways. The profiles were applied to discrete stages of in vitro differentiation of mouse embryonic stem cells toward the dopaminergic lineage and after transplantation into the striatum of 6-hydroxy-dopamine-lesioned rats. The comparison of gene expression in vitro with stages in the developing ventral midbrain between embryonic day 11.5 and 13.5 ex vivo revealed dynamic changes in the expression of transcription factors and signaling molecules. Based on these profiles, we propose quantitative gene expression milestones that predict the efficiency of dopaminergic differentiation achieved at the end point of the protocol, already at earlier stages of differentiation.<\/jats:p>","DOI":"10.1089\/scd.2012.0238","type":"journal-article","created":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T12:36:17Z","timestamp":1344861377000},"page":"397-411","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Expression of Early Developmental Markers Predicts the Efficiency of Embryonic Stem Cell Differentiation into Midbrain Dopaminergic Neurons"],"prefix":"10.1177","volume":"22","author":[{"given":"Ahmad","family":"Salti","sequence":"first","affiliation":[{"name":"Innsbruck Medical University","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Nat","sequence":"additional","affiliation":[{"name":"Innsbruck Medical University","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonya","family":"Neto","sequence":"additional","affiliation":[{"name":"Innsbruck Medical University","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoe","family":"Puschban","sequence":"additional","affiliation":[{"name":"Innsbruck Medical University","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregor","family":"Wenning","sequence":"additional","affiliation":[{"name":"Innsbruck Medical University","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Dechant","sequence":"additional","affiliation":[{"name":"Innsbruck Medical University","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,8,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/76536"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt870"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00900"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712359105"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0365"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-1-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2039"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.01.032"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.12.017"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35053516"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1195-1184"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81437-3"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(00)00161-7"},{"key":"e_1_3_3_15_2","first-page":"646","article-title":"Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway","volume":"5","author":"Chung S","year":"2009","unstructured":"Chung S, , Leung A, , Han B-S, , Chang M-Y, , Moon J-I et al. 2009. 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