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They propagate by recruiting host\u2010encoded PrP\n                    <jats:sup>C<\/jats:sup>\n                    although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrP\n                    <jats:sup>C<\/jats:sup>\n                    expression differences, to identify such factors. Transcriptome analysis of prion\u2010resistant revertants, isolated from highly susceptible cells, revealed a gene expression signature associated with susceptibility and modulated by differentiation. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease\u2010related PrP is deposited. Silencing nine of these genes significantly increased susceptibility. Silencing of\n                    <jats:italic>Papss2<\/jats:italic>\n                    led to undersulphated heparan sulphate and increased PrP\n                    <jats:sup>C<\/jats:sup>\n                    deposition at the ECM, concomitantly with increased prion propagation. Moreover, inhibition of fibronectin 1 binding to integrin \u03b18 by RGD peptide inhibited metalloproteinases (MMP)\u20102\/9 whilst increasing prion propagation. In summary, we have identified a gene regulatory network associated with prion propagation at the ECM and governed by the cellular differentiation state.\n                  <\/jats:p>","DOI":"10.15252\/embj.201387150","type":"journal-article","created":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T00:13:17Z","timestamp":1400544797000},"page":"1527-1547","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Identification of a gene regulatory network associated with prion replication"],"prefix":"10.1038","volume":"33","author":[{"given":"Masue M","family":"Marbiah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy T","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anais","family":"Louzolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Alden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Grigoriadis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Hummerich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho\u2010Man","family":"Kan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S","family":"Bloom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parmjit","family":"Jat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u2010Christian","family":"Kl\u00f6hn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,5,19]]},"reference":[{"key":"BFEMBJ201387150_CR1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0008-6363(00)00312-6","volume":"49","author":"DI Axel","year":"2001","unstructured":"Axel DI, Frigge A, Dittmann J, Runge H, Spyridopoulos I, Riessen R, Viebahn R, Karsch KR (2001) All\u2010trans retinoic acid regulates proliferation, migration, differentiation, and extracellular matrix turnover of human arterial smooth muscle cells. 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