Pluripotent reprogramming arises from a unique subset of pre-disposed human dermal fibroblasts. Homo sapiens

Induced cellular reprogramming to the pluripotent state offers a novel stem cell source for autologous transplantation. While recent studies have explored the role of factors required for induced pluripotent stem cell (iPSC) induction, the cellular and molecular basis of reprogramming from human fibroblasts remains elusive. Here, we have identified a subset of human dermal-derived fibroblasts that shares hallmark molecular and epigenetic features with pluripotent cells. Functional studies demonstrate that these cells contribute to the majority of human iPSCs generated from dermal fibroblasts and are dependent on heterogeneous fibroblast microenvironment for reprogramming competency. Molecular characterization indicated these predisposed fibroblasts were unique to other dermal derived stem cells and possessed features of proliferative selfrenewal. Our study reveals human fibroblasts are not equivalently capable of cellular reprogramming, and suggests that reprogramming factors overcome commitment steps that allow predetermined dermal fibroblasts to establish stable pluripotent state. Overall design: Samples were obtained from human dermal fibroblasts (hFibs) transduced with a EOS lentiviral vector containing trimerized Oct4 enhancer elements that allow expression of GFP. Upon EOS transduction, we observed a small frequency of adult breast-derived dermal fibroblasts expressing GFP, fibroblasts were sorted based on GFP expression on FACS Aria (BD Pharmagin). 2 samples of GFP-positive and 2 samples of GFP-negative cells from transduced dermal fibroblasts and 1 sample of skin-derived precursors were obtained for this study.