讲座题目: A Blueprint for Cell Fate: Network Biology Applied to Stem Cell Engineering

主讲人: Samantha Morris, Boston Children’s Hospital and Harvard Medical School, USA

主持人:王媛 教授

开始时间:2014-10-30 15:30

讲座地址:闵行生科院534报告厅

 

报告人简介：Samantha Morris is a Postdoctoral Fellow of Boston Children’s Hospital, Harvard Medical School. In 2006 he obtained his Ph. D in the department of Oncology, Clare College, University of Cambridge, UK. From 2007 July to 2011 October, he was a postdoctoral Fellow in Gurdon Institute, Department of Physiology, Development and Neuroscience, University of Cambridge, UK.

 

报告摘要：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. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed long-term functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells.