Identification of a combination of transcription factors that synergistically increases endothelial cell barrier resistance.

Scientific Reports
Filip RoudnickyChad A Cowan

Abstract

Endothelial cells (ECs) display remarkable plasticity during development before becoming quiescent and functionally mature. EC maturation is directed by several known transcription factors (TFs), but the specific set of TFs responsible for promoting high-resistance barriers, such as the blood-brain barrier (BBB), have not yet been fully defined. Using expression mRNA data from published studies on ex vivo ECs from the central nervous system (CNS), we predicted TFs that induce high-resistance barrier properties of ECs as in the BBB. We used our previously established method to  generate ECs from human pluripotent stem cells (hPSCs), and then we overexpressed the candidate TFs in hPSC-ECs and measured barrier resistance and integrity using electric cell-substrate impedance sensing, trans-endothelial electrical resistance and FITC-dextran permeability assays. SOX18 and TAL1 were the strongest EC barrier-inducing TFs, upregulating Wnt-related signaling and EC junctional gene expression, respectively, and downregulating EC proliferation-related genes. These TFs were combined with SOX7 and ETS1 that together effectively induced EC barrier resistance, decreased paracellular transport and increased protein expression of tight junctions...Continue Reading

References

Jan 1, 1985·Annual Review of Genetics·K R Yamamoto
Mar 1, 1994·Brain Research. Molecular Brain Research·R J BoadoW M Pardridge
Jun 6, 2000·Advanced Drug Delivery Reviews·A H Schinkel
May 14, 2003·The Journal of Cell Biology·Takehiro NittaShoichiro Tsukita
Sep 1, 2004·Biochemical and Biophysical Research Communications·Mutsumi KanamoriHarukazu Suzuki
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jun 3, 2008·Nature Methods·Ali MortazaviBarbara Wold
Jun 21, 2008·Journal of Cell Science·Elisabetta DejanaMaria Grazia Lampugnani
Oct 29, 2008·The Journal of Cell Biology·Stefan LiebnerElisabetta Dejana
Jan 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Richard DanemanBen A Barres
Jun 6, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ruth LyckFrancois Verrey
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Feb 24, 2010·In Vitro Cellular & Developmental Biology. Animal·Mikael C O EnglundJohan Hyllner
Mar 10, 2010·Cell·Timothy RavasiYoshihide Hayashizaki
Aug 10, 2010·BMC Research Notes·Emma Laing, Colin P Smith
Aug 26, 2010·Molecular Pharmaceutics·Anne Mahringer, Gert Fricker
Feb 9, 2012·Cold Spring Harbor Perspectives in Medicine·William C Aird
Feb 22, 2012·Developmental Cell·Stephen J TamRyan J Watts
Sep 11, 2012·Cell·Shane NephJohn A Stamatoyannopoulos
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 12, 2013·Fluids and Barriers of the CNS·Kathrin BensonHans-Joachim Galla
Apr 27, 2013·Circulation Research·Kathrina L MarceloKaren K Hirschi
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Mar 11, 2015·The Journal of Cell Biology·Olga TornavacaMaria S Balda
Jul 28, 2015·Nature Cell Biology·Christoph PatschChad A Cowan
Apr 21, 2016·Science Signaling·Yuqi CaiVladimir V Kalinichenko
Oct 14, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Yang LinMervin C Yoder
Dec 20, 2017·Molecular Metabolism·Alessandro Di SpiezioMarkus Schwaninger
Nov 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Yanshu WangJeremy Nathans
May 28, 2019·Methods in Molecular Biology·Klaus ChristensenChristoph Patsch

❮ Previous
Next ❯

Citations

Sep 26, 2020·Advanced Healthcare Materials·Héloïse RagellePeter D Westenskow
Sep 22, 2020·Current Protocols in Stem Cell Biology·Antje Appelt-MenzelOle Pless
Sep 10, 2020·Life Science Alliance·Najwa Ouali AlamiFrancesco Roselli
Jan 6, 2021·International Journal of Molecular Sciences·Alexander OuNazanin Majd
Feb 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Tyler M LuRaphaël Lis
Apr 20, 2021·Frontiers in Physiology·Tyler M LuRaphaël Lis
Jun 4, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yukihiro HaradaOsamu Nakagawa
Jul 2, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Iohanna DeckmannCarmem Gottfried

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
Fluorescence

Software Mentioned

Prism
ImageJ
Gene Set Enrichment Analysis ( GSEA )
GraphPad
SAMtools
ECIS
GSEA
RankProdit
TEER
STAR

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.