title: Enhancing mammary differentiation by overcoming lineage-specific epigenetic modification and signature gene expression of fibroblast-derived iPSCs.
abstract: Recent studies have shown that induced pluripotent stem cells (iPSCs) retain a memory of their origin and exhibit biased differentiation potential. This finding reveals a severe limitation in the application of iPSCs to cell-based therapy because it means that certain cell types are not available for reprogramming for patients. Here we show that the iPSC differentiation process is accompanied by profound gene expression and epigenetic modifications that reflect cells' origins. Under typical conditions for mammary differentiation, iPSCs reprogrammed from tail-tip fibroblasts (TF-iPSCs) activated a fibroblast-specific signature that was not compatible with mammary differentiation. Strikingly, under optimized conditions, including coculture with iPSCs derived from the mammary epithelium or in the presence of pregnancy hormones, the fibroblast-specific signature of TF-iPSCs obtained during differentiation was erased and cells displayed a mammary-specific signature with a markedly enhanced ability for mammary differentiation. These findings provide new insights into the precise control of differentiation conditions that may have applications in personalized cell-based therapy.
authors.affiliation: 1] Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, Bethesda, MD, USA [2] Xin-Qiao Hospital, The Third Military Medical University, Chongqing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, Bethesda, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Hong
authors.affiliation: Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, Bethesda, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Microarray Core Facility, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: 1] Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, Bethesda, MD, USA [2] Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: R-H
authors.initials: RH
authors.lastname: Wang
authors.affiliation: 1] Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, Bethesda, MD, USA [2] Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Xu
authors.affiliation: 1] Genetics of Development and Disease Branch, NIDDK/NIH, 10/9N105, Bethesda, MD, USA [2] Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: C-X
authors.initials: CX
authors.lastname: Deng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects / Q000235:genetics*; D018920:Coculture Techniques; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D059467:Transcriptome
chemical_list: D004967:Estrogens; D011374:Progesterone