Enhancing Mammary Differentiation by Overcoming Lineage Specific Epigenetic Modification and Signature Gene Expression of Fibroblast Derived iPSCs
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ABSTRACT: Recent studies showed that Induced pluripotent stem cells (iPSCs) could hold memory of their origin and exhibit skewed differentiation potential. This finding reveals a severe limit for the application of iPSCs in cell-based therapy in case certain cell types are not available for reprograming from patients. Here we show that under a typical condition for mammary differentiation, iPSCs derived from mouse mammary epithelium cells (ME-iPSCs) exhibit mammary signature gene expression and chromatin epigenetic modification, leading to smooth progress for mammary gland formation. In contrast, iPSCs reprogramed from tail fibroblasts (TF-iPSCs) displayed fibroblast specific signature that is not compatible for mammary differentiation both in vitro and in vivo. Strikingly, when co-culturing with ME-iPSCs or under pregnant condition, the fibroblast specific signature of TF-iPSCs was erased and the cells gained enhanced ability for mammary differentiation. These findings provide new insights into the precise control of differentiation conditions for future personalized cell-based therapy.
ORGANISM(S): Mus musculus
PROVIDER: GSE38471 | GEO | 2015/05/28
SECONDARY ACCESSION(S): PRJNA168028
REPOSITORIES: GEO
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