title: Converting stem cells to dendritic cells by agonist antibodies from unbiased morphogenic selections.
abstract: When combinatorial antibody libraries are rendered infectious for eukaryotic cells, the integrated antibody genotype and cellular phenotype become permanently linked and each cell becomes a selection system unto itself. These systems should be ideal for the identification of proteins and pathways that regulate differentiation so long as selection systems can be devised. Here we use a selection system based on the ability of secreted antibodies to alter the morphology of colonies expressing them when grown in soft agar. Importantly, this approach is different from all previous studies in that it used a pure discovery format where unbiased libraries that were not preselected against any known protein were used as probes. As such, the strategy is analogous to classical forward genetic approaches except that it operates directly at the protein level. This approach led to the identification of integrin-binding agonist antibodies that efficiently converted human stem cells to dendritic cells.
authors: The Scripps Korea Antibody Institute, Chuncheon-si 200-701, South Korea.
authors: Kyungmoo
authors: K
authors: Yea
authors: Hongkai
authors: H
authors: Zhang
authors: Jia
authors: J
authors: Xie
authors: Teresa M
authors: TM
authors: Jones
authors: Guang
authors: G
authors: Yang
authors: Byeong Doo
authors: BD
authors: Song
authors: Richard A
authors: RA
authors: Lerner
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage; D022801:Complementarity Determining Regions / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D019143:Evolution, Molecular; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D019151:Peptide Library
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions; D016023:Integrins; D009842:Oligopeptides; D019151:Peptide Library; C047981:arginyl-glycyl-aspartic acid
keywords: intracellular combinatorial antibodies; phenotypic selections
references: Annu Rev Cell Dev Biol. 1996;12:697-715
references: 8970741
references: Curr Biol. 1997 Sep 1;7(9):682-8
references: 9285722
references: Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6385-9
references: 8341642
references: Stem Cell Res. 2008 Sep;1(3):205-18
references: 19383401
references: EMBO J. 1996 Aug 15;15(16):4174-81
references: 8861946
references: Genomics. 1992 Apr;12(4):788-94
references: 1374051
references: Cell. 2006 Aug 25;126(4):677-89
references: 16923388
references: Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1391-6
references: 21220345
references: Blood Cells. 1994;20(2-3):411-23
references: 7538347
references: Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3557-62
references: 14990803
references: Oncogene. 2002 May 13;21(21):3295-313
references: 12032771
references: Blood. 1993 May 15;81(10):2579-84
references: 7683923
references: Annu Rev Biophys. 2012;41:519-42
references: 22404680
references: Cancer Res. 2009 Aug 15;69(16):6515-21
references: 19638574
references: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8099-104
references: 23613575
references: J Leukoc Biol. 2002 Mar;71(3):425-32
references: 11867680
references: Nature. 2011 Jul 20;475(7356):316-23
references: 21776077
references: Chem Biol. 2013 May 23;20(5):734-41
references: 23706638
references: Nature. 2007 Oct 25;449(7165):1073-7
references: 17960246
references: Cell Stem Cell. 2012 Apr 6;10(4):440-54
references: 22482508
references: Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15728-33
references: 23019357
references: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17210-5
references: 15563590
references: Dev Biol. 2005 Apr 15;280(2):260-80
references: 15882572
references: Int J Hematol. 2007 Jun;85(5):384-9
references: 17562612
references: J Biol Chem. 2005 Sep 30;280(39):33610-9
references: 15955823
references: Biochem Soc Trans. 2004 Jun;32(Pt3):438-42
references: 15157155
references: Mol Cell Biol. 1997 Aug;17(8):4406-18
references: 9234699
references: Science. 1999 Aug 13;285(5430):1028-32
references: 10446041
references: Science. 2010 Sep 10;329(5997):1345-8
references: 20688981
references: Cell. 2007 Nov 30;131(5):861-72
references: 18035408
references: J Endocrinol. 2011 May;209(2):139-51
references: 21307119
references: J Cell Physiol. 1989 Aug;140(2):323-34
references: 2663885
references: Nat Cell Biol. 2011 May;13(5):497-505
references: 21540845
references: Cancer Res. 1988 Mar 15;48(6):1566-70
references: 2449954