title: Profile of Inflammation-associated genes during Hepatic Differentiation of Human Pluripotent Stem Cells.
abstract: Expression of genes associated with inflammation was analyzed during differentiation of human pluripotent stem cells (PSCs) to hepatic cells. Messenger RNA transcript profiles of differentiated endoderm (day 5), hepatoblast (day 15) and hepatocyte-like cells (day 21) were obtained by RNA sequencing analysis. When compared to endoderm cells an immature cell type, the hepatic cells (days 15 and 21) had significantly higher expression of acute phase protein genes including complement factors, coagulation factors, serum amyloid A and serpins. Furthermore, hepatic phase of cells expressed proinflammatory cytokines IL18 and IL32 as well as cytokine receptors IL18R1, IL1R1, IL1RAP, IL2RG, IL6R, IL6ST and IL10RB. These cells also produced CCL14, CCL15, and CXCL- 1, 2, 3, 16 and 17 chemokines. Endoderm cells had higher levels of chemokine receptors, CXCR4 and CXCR7, than that of hepatic cells. Sirtuin family of genes involved in aging, inflammation and metabolism were differentially regulated in endoderm and hepatic phase cells. Ligands and receptors of the tumor necrosis factor (TNF) family as well as downstream signaling factors TRAF2, TRAF4, FADD, NFKB1 and NFKBIB were differentially expressed during hepatic differentiation.
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ignatius Irudayam
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Deisy
authors.initials: D
authors.lastname: Contreras
authors.affiliation: Cedars-Sinai Genomics Core, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Spurka
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Songyang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Kanagavel
authors.affiliation: Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, Karnataka 560012, India ; Hindustan Genomics Institute, SVA Medical Center, Kadayam, Tamil Nadu 627415, India.
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Ramaiah
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Alagappan
authors.initials: A
authors.lastname: Annamalai
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA ; Department of Surgery, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Klein
authors.affiliation: Cedars-Sinai Genomics Core, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Funari
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA ; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA ; Department of Surgery, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Vaithilingaraja
authors.initials: V
authors.lastname: Arumugaswami
keywords: SIRT1; cytokines; differential gene expression; differentiation; endoderm; hepatic cells; hepatoblast; hepatocytes; inflammation; pluripotent stem cells; sirtuin