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The need to derive and culture diverse cell or tissue types in vitro has prompted investigations on how changes in culture conditions affect cell states. However, the identification of the optimal conditions (e.g., signaling molecules and growth factors) required to maintain cell types or convert between cell types remains a time-consuming task. Here, we developed EpiMogrify, an approach that leverages data from ∼100 human cell/tissue types available from ENCODE and Roadmap Epigenomics consortia to predict signaling molecules and factors that can either maintain cell identity or enhance directed differentiation (or cell conversion). EpiMogrify integrates protein-protein interaction network information with a model of the cell's epigenetic landscape based on H3K4me3 histone modifications. Using EpiMogrify-predicted factors for maintenance conditions, we were able to better potentiate the maintenance of astrocytes and cardiomyocytes in vitro. We report a significant increase in the efficiency of astrocyte and cardiomyocyte differentiation using EpiMogrify-predicted factors for conversion conditions., Competing Interests: Declaration of Interests O.J.L.R., E.P., U.S.K., J.M.P., and J.C. have filed a patent (PCT application no: PCT/AU, 2020/050656 titled “Cell Culture Methods and Compositions” filed on June 26, 2020). There are restrictions to the availability of some predicted culture conditions and EpiMogrify code, as they are subject to the patent application and are under commercial investigation. O.J.L.R. and J.M.P. are also co-inventors of the patent (WO/2017/106932) and are co-founders, scientific advisory board members, and shareholders of Mogrify Ltd, a cell therapy company. All other authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)