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      CellNet: Network Biology Applied to Stem Cell Engineering

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      Cell

      Elsevier BV

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          Abstract

          Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          00928674
          August 2014
          August 2014
          : 158
          : 4
          : 903-915
          Article
          10.1016/j.cell.2014.07.020
          25126793
          © 2014

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