10.3389/fmicb.2019.00127.s002 Rebecca E. Tweedell Rebecca E. Tweedell Dingyin Tao Dingyin Tao Timothy Hamerly Timothy Hamerly Tanisha M. Robinson Tanisha M. Robinson Simon Larsen Simon Larsen Alexander G. B. Grønning Alexander G. B. Grønning Alessandra M. Norris Alessandra M. Norris Jonas G. King Jonas G. King Henry Chun Hin Law Henry Chun Hin Law Jan Baumbach Jan Baumbach Elke S. Bergmann-Leitner Elke S. Bergmann-Leitner Rhoel R. Dinglasan Rhoel R. Dinglasan Table_1_The Selection of a Hepatocyte Cell Line Susceptible to Plasmodium falciparum Sporozoite Invasion That Is Associated With Expression of Glypican-3.XLSX Frontiers 2019 malaria Plasmodium falciparum liver stage in vitro model omics glypican-3 hepatocyte 2019-02-28 04:12:22 Dataset https://frontiersin.figshare.com/articles/dataset/Table_1_The_Selection_of_a_Hepatocyte_Cell_Line_Susceptible_to_Plasmodium_falciparum_Sporozoite_Invasion_That_Is_Associated_With_Expression_of_Glypican-3_XLSX/7781360 <p>In vitro studies of liver stage (LS) development of the human malaria parasite Plasmodium falciparum are technically challenging; therefore, fundamental questions about hepatocyte receptors for invasion that can be targeted to prevent infection remain unanswered. To identify novel receptors and to further understand human hepatocyte susceptibility to P. falciparum sporozoite invasion, we created an optimized in vitro system by mimicking in vivo liver conditions and using the subcloned HC-04.J7 cell line that supports mean infection rates of 3–5% and early development of P. falciparum exoerythrocytic forms—a 3- to 5-fold improvement on current in vitro hepatocarcinoma models for P. falciparum invasion. We juxtaposed this invasion-susceptible cell line with an invasion-resistant cell line (HepG2) and performed comparative proteomics and RNA-seq analyses to identify host cell surface molecules and pathways important for sporozoite invasion of host cells. We identified and investigated a hepatocyte cell surface heparan sulfate proteoglycan, glypican-3, as a putative mediator of sporozoite invasion. We also noted the involvement of pathways that implicate the importance of the metabolic state of the hepatocyte in supporting LS development. Our study highlights important features of hepatocyte biology, and specifically the potential role of glypican-3, in mediating P. falciparum sporozoite invasion. Additionally, it establishes a simple in vitro system to study the LS with improved invasion efficiency. This work paves the way for the greater malaria and liver biology communities to explore fundamental questions of hepatocyte-pathogen interactions and extend the system to other human malaria parasite species, like P. vivax.</p>