title: Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage.
abstract: During the reprogramming of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells, the activation of pluripotency genes such as NANOG occurs after the mesenchymal to epithelial transition. Here we report that both adult stem cells (neural stem cells) and differentiated cells (astrocytes) of the neural lineage can activate NANOG in the absence of cadherin expression during reprogramming. Gene expression analysis revealed that only the NANOG+E-cadherin+ populations expressed stabilization markers, had upregulated several cell cycle genes; and were transgene independent. Inhibition of DOT1L activity enhanced both the numbers of NANOG+ and NANOG+E-cadherin+ colonies in neural stem cells. Expressing SOX2 in MEFs prior to reprogramming did not alter the ratio of NANOG colonies that express E-cadherin. Taken together these results provide a unique pathway for reprogramming taken by cells of the neural lineage.
authors.affiliation: Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Jackson
authors.affiliation: Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA.
authors.forename: Zachariah P G
authors.initials: ZP
authors.lastname: Olufs
authors.affiliation: Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA.
authors.forename: Khoa A
authors.initials: KA
authors.lastname: Tran
authors.affiliation: Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA.
authors.forename: Nur Zafirah
authors.initials: NZ
authors.lastname: Zaidan
authors.affiliation: Epigenetics Theme, Wisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin, 1111 Highland Avenue, Madison, WI 53715, USA. Electronic address: rsridharan@discovery.wisc.edu.
authors.forename: Rupa
authors.initials: R
authors.lastname: Sridharan
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D011495:Histone-Lysine N-Methyltransferase; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D000071317:Nanog Homeobox Protein; D055748:SOXB1 Transcription Factors; C481527:Dot1l protein, mouse; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase