{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:37:27Z","timestamp":1790735847659,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melanin is a black\/brown pigment present in abundance in human skin. Its main function is photo-protection of underlying tissues from harmful UV light. Natural sources of isolated human melanin are limited; thus, in vitro cultures of human cells may be a promising source of human melanin. Here, we present an innovative in vitro differentiation protocol of induced pluripotent stem cells (iPS) into melanin-producing cells, delivering highly pigmented cells in quantity and quality incomparably higher than any other methods previously described. Pigmented cells constitute over 90% of a terminally differentiated population and exhibit features characteristic for melanocytes, i.e., expression of specific markers such as MITF-M (microphthalmia-associated transcription factor isoform M), TRP-1 (tyrosinase-related protein 1), and TYR (tyrosinase) and accumulation of black pigment in organelles closely resembling melanosomes. Black pigment is unambiguously identified as melanin with features corresponding to those of melanin produced by typical melanocytes. The advantage of our method is that it does not require any sophisticated procedures and can be conducted in standard laboratory conditions. Moreover, our protocol is highly reproducible and optimized to generate high-purity melanin-producing cells from iPS cells; thus, it can serve as an unlimited source of human melanin for modeling human skin diseases. We speculate that FGF-8 might play an important role during differentiation processes toward pigmented cells.<\/jats:p>","DOI":"10.3390\/ijms222312787","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:22:28Z","timestamp":1638314548000},"page":"12787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Highly Effective Protocol for Differentiation of Induced Pluripotent Stem Cells (iPS) into Melanin-Producing Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-8258","authenticated-orcid":false,"given":"Maciej","family":"Su\u0142kowski","sequence":"first","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-0411","authenticated-orcid":false,"given":"Marta","family":"Kot","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogna","family":"Badyra","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Paluszkiewicz","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0261-3439","authenticated-orcid":false,"given":"Przemys\u0142aw M.","family":"P\u0142onka","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9306-7965","authenticated-orcid":false,"given":"Micha\u0142","family":"Sarna","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Michalczyk-Wetula","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1230-1129","authenticated-orcid":false,"given":"Fabio A.","family":"Zucca","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Technologies, National Research Council of Italy, 20054 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Zecca","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Technologies, National Research Council of Italy, 20054 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0429-681X","authenticated-orcid":false,"given":"Marcin","family":"Majka","sequence":"additional","affiliation":[{"name":"Department of Transplantation, Faculty of Medicine, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/emmm.201200215","article-title":"Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson\u2019s disease","volume":"4","author":"Caig","year":"2012","journal-title":"EMBO Mol. 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