title: Vascular regeneration in a basal chordate is due to the presence of immobile, bi-functional cells.
abstract: The source of tissue turnover during homeostasis or following injury is usually due to proliferation of a small number of resident, lineage-restricted stem cells that have the ability to amplify and differentiate into mature cell types. We are studying vascular regeneration in a chordate model organism, Botryllus schlosseri, and have previously found that following surgical ablation of the extracorporeal vasculature, new tissue will regenerate in a VEGF-dependent process within 48 hrs. Here we use a novel vascular cell lineage tracing methodology to assess regeneration in parabiosed individuals and demonstrate that the source of regenerated vasculature is due to the proliferation of pre-existing vascular resident cells and not a mobile progenitor. We also show that these cells are bi-potential, and can reversibly adopt two fates, that of the newly forming vessels or the differentiated vascular tissue at the terminus of the vasculature, known as ampullae. In addition, we show that pre-existing vascular resident cells differentially express progenitor and differentiated cell markers including the Botryllus homologs of CD133, VEGFR-2, and Cadherin during the regenerative process.
authors.affiliation: Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Braden
authors.affiliation: Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Taketa
authors.affiliation: Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: James D
authors.initials: JD
authors.lastname: Pierce
authors.affiliation: Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: Susannah
authors.initials: S
authors.lastname: Kassmer
authors.affiliation: Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Lewis
authors.affiliation: Department of Molecular, Cellular, Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: De Tomaso
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology* / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000378:metabolism; D012038:Regeneration; D013269:Stochastic Processes; D014561:Urochordata / Q000166:cytology* / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D015820:Cadherins; D006023:Glycoproteins; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2
references.citation: Nat Med. 2003 Jun;9(6):702-12
references.pmid: 12778169
references.citation: Curr Biol. 2001 May 1;11(9):644-51
references.pmid: 11369227
references.citation: Nat Methods. 2009 Feb;6(2):153-9
references.pmid: 19169259
references.citation: Dev Biol. 2007 Apr 15;304(2):687-700
references.pmid: 17316601
references.citation: Dev Dyn. 2007 Mar;236(3):719-31
references.pmid: 17256755
references.citation: Dev Biol. 2013 Mar 15;375(2):182-92
references.pmid: 23201012
references.citation: PLoS One. 2013 Jun 24;8(6):e65980
references.pmid: 23826085
references.citation: Dev Dyn. 2007 Feb;236(2):335-52
references.pmid: 17191252
references.citation: Cell Mol Life Sci. 2010 Oct;67(19):3209-18
references.pmid: 20490602
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6620-5
references.pmid: 18443294
references.citation: Dev Biol. 2002 Sep 15;249(2):333-48
references.pmid: 12221010
references.citation: Nature. 2009 Jul 2;460(7251):60-5
references.pmid: 19571878
references.citation: Trends Cardiovasc Med. 2006 Feb;16(2):55-9
references.pmid: 16473763
references.citation: N Engl J Med. 2003 Feb 13;348(7):593-600
references.pmid: 12584367
references.citation: Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9148-53
references.pmid: 10430910
references.citation: EMBO J. 2012 Feb 15;31(4):842-55
references.pmid: 22179698
references.citation: Cell Stem Cell. 2010 Dec 3;7(6):656-70
references.pmid: 21112561
references.citation: Science. 1997 Feb 14;275(5302):964-7
references.pmid: 9020076
references.citation: Stem Cells Dev. 2013 Apr 1;22(7):1018-26
references.pmid: 23330734
references.citation: Annu Rev Med. 2007;58:299-312
references.pmid: 17076602
references.citation: Stem Cell Rev. 2008 Spring;4(1):27-49
references.pmid: 18288619
references.citation: Blood. 2000 Feb 1;95(3):952-8
references.pmid: 10648408
references.citation: Dev Comp Immunol. 2013 Oct;41(2):128-36
references.pmid: 23542705
references.citation: Nature. 2006 Feb 23;439(7079):965-8
references.pmid: 16495997
references.citation: Biol Bull. 1967 Apr;132(2):229-243
references.pmid: 29332443
references.citation: Angiogenesis. 2013 Apr;16(2):405-16
references.pmid: 23150059
references.citation: Nature. 1975 Sep 18;257(5523):224-5
references.pmid: 1161022
references.citation: J Gastroenterol Hepatol. 2011 Jan;26 Suppl 1:203-12
references.pmid: 21199532
references.citation: Dev Comp Immunol. 2010 Mar;34(3):272-85
references.pmid: 19837108
references.citation: Prog Cardiovasc Dis. 2007 Jul-Aug;50(1):31-48
references.pmid: 17631436
references.citation: Dev Biol. 2013 Feb 15;374(2):357-73
references.pmid: 23174529
references.citation: J Histochem Cytochem. 2008 Nov;56(11):977-93
references.pmid: 18645205
references.citation: Stem Cells. 2005 Jun-Jul;23(6):791-804
references.pmid: 15917475
references.citation: Dev Growth Differ. 2007 Feb;49(2):155-61
references.pmid: 17335436
references.citation: Nature. 2010 Mar 25;464(7288):601-5
references.pmid: 20336144
references.citation: Evol Dev. 2008 Sep-Oct;10(5):591-605
references.pmid: 18803777
references.citation: J Morphol. 1978 Jul;157(1):49-77
references.pmid: 30227698
references.citation: Dev Dyn. 2011 Mar;240(3):674-81
references.pmid: 21337465
references.citation: Int J Dev Biol. 2011;55(4-5):345-51
references.pmid: 21732276
references.citation: Autophagy. 2008 Apr;4(3):322-9
references.pmid: 18216495
references.citation: Annu Rev Med. 2005;56:79-101
references.pmid: 15660503
references.citation: Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):288-93
references.pmid: 14699017
references.citation: Nature. 2010 Nov 11;468(7321):310-5
references.pmid: 21068842
references.citation: Immunity. 2011 Apr 22;34(4):616-26
references.pmid: 21497115
references.citation: Microvasc Res. 2010 May;79(3):162-8
references.pmid: 20043930
references.citation: Dev Biol. 2008 Mar 1;315(1):243-55
references.pmid: 18234178
references.citation: Dev Cell. 2011 Jul 19;21(1):172-85
references.pmid: 21763617
references.citation: Cell. 2011 Jun 10;145(6):851-62
references.pmid: 21663791
references.citation: J Mol Cell Cardiol. 2011 Feb;50(2):304-11
references.pmid: 20850452
references.citation: Science. 2013 Jul 26;341(6144):384-7
references.pmid: 23888037
references.citation: Cell. 2005 Dec 29;123(7):1351-60
references.pmid: 16377573
references.citation: Nature. 2011 Aug 24;476(7361):409-13
references.pmid: 21866153
references.citation: Nature. 2010 Mar 25;464(7288):606-9
references.pmid: 20336145
references.citation: Immunity. 2006 Jul;25(1):163-73
references.pmid: 16860765
references.citation: Cell. 2008 Feb 22;132(4):697-710
references.pmid: 18295584
references.citation: J Cell Biol. 2012 Mar 5;196(5):553-62
references.pmid: 22391035