title: Expression of podocalyxin separates the hematopoietic and vascular potentials of mouse embryonic stem cell-derived mesoderm.
abstract: In the mouse embryo and differentiating embryonic stem cells, the hematopoietic, endothelial, and cardiomyocyte lineages are derived from Flk1+ mesodermal progenitors. Here, we report that surface expression of Podocalyxin (Podxl), a member of the CD34 family of sialomucins, can be used to subdivide the Flk1+ cells in differentiating embryoid bodies at day 4.75 into populations that develop into distinct mesodermal lineages. Definitive hematopoietic potential was restricted to the Flk1+Podxl+ population, while the Flk1-negative Podxl+ population displayed only primitive erythroid potential. The Flk1+Podxl-negative population contained endothelial cells and cardiomyocyte potential. Podxl expression distinguishes Flk1+ mesoderm populations in mouse embryos at days 7.5, 8.5, and 9.5 and is a marker of progenitor stage primitive erythroblasts. These findings identify Podxl as a useful tool for separating distinct mesodermal lineages.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA; The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA.
authors.forename: Hailan
authors.initials: H
authors.lastname: Zhang
authors.forename: Johnathan L
authors.initials: JL
authors.lastname: Nieves
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Fraser
authors.forename: Joan
authors.initials: J
authors.lastname: Isern
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Douvaras
authors.forename: Dmitri
authors.initials: D
authors.lastname: Papatsenko
authors.forename: Sunita L
authors.initials: SL
authors.lastname: D'Souza
authors.forename: Ihor R
authors.initials: IR
authors.lastname: Lemischka
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dyer
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Baron
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D012795:Sialoglycoproteins; C001643:podocalyxin
keywords: Endothelial cell; Flk1; Gastrulation; Hematopoiesis; Mesoderm induction; Mouse embryonic stem cells; Pluripotent cells; Podocalyxin; Vascular development
references.citation: Blood. 2005 Jun 1;105(11):4170-8
references.pmid: 15701716
references.citation: J Biol Chem. 1993 Nov 25;268(33):25244-52
references.pmid: 8227090
references.citation: J Cell Biol. 1997 Sep 22;138(6):1395-407
references.pmid: 9298993
references.citation: J Am Soc Nephrol. 2009 Aug;20(8):1669-76
references.pmid: 19578008
references.citation: Nat Biotechnol. 2008 Oct;26(10):1169-78
references.pmid: 18820686
references.citation: Development. 1998 May;125(9):1747-57
references.pmid: 9521912
references.citation: Methods Mol Med. 2005;105:231-56
references.pmid: 15492399
references.citation: Genes Dev. 2005 May 15;19(10):1129-55
references.pmid: 15905405
references.citation: Cell Stem Cell. 2007 Dec 13;1(6):635-45
references.pmid: 18371405
references.citation: Dev Cell. 2009 Feb;16(2):180-95
references.pmid: 19217421
references.citation: Stem Cells. 2013 Sep;31(9):1893-901
references.pmid: 23712751
references.citation: Methods Enzymol. 2010;476:403-27
references.pmid: 20691878
references.citation: J Cell Biol. 1986 Feb;102(2):484-91
references.pmid: 3511072
references.citation: Mol Biol Cell. 2000 Sep;11(9):3219-32
references.pmid: 10982412
references.citation: Stem Cells. 2008 Feb;26(2):401-11
references.pmid: 17991917
references.citation: Development. 2003 Sep;130(17):4217-27
references.pmid: 12874139
references.citation: Development. 1991 Nov;113(3):891-911
references.pmid: 1821858
references.citation: Dev Cell. 2006 Nov;11(5):723-32
references.pmid: 17084363
references.citation: J Exp Med. 1998 Jun 15;187(12):1965-75
references.pmid: 9625756
references.citation: Immunity. 1999 Nov;11(5):567-78
references.pmid: 10591182
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9127-32
references.pmid: 10922068
references.citation: Development. 2007 Aug;134(16):3041-8
references.pmid: 17634194
references.citation: Stem Cells. 2009 Dec;27(12):2884-95
references.pmid: 19711456
references.citation: Blood. 2012 Jun 7;119(23):5417-28
references.pmid: 22535663
references.citation: Genes Dev. 1997 Apr 15;11(8):1048-60
references.pmid: 9136932
references.citation: Blood. 2011 Dec 22;118(26):6975-86
references.pmid: 21911838
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13170-5
references.pmid: 16141334
references.citation: Development. 1999 Nov;126(21):4691-701
references.pmid: 10518487
references.citation: Blood. 2003 Mar 1;101(5):1669-76
references.pmid: 12406884
references.citation: Blood. 2009 Jan 15;113(3):563-6
references.pmid: 18957687
references.citation: J Exp Med. 2001 Jul 2;194(1):13-27
references.pmid: 11435469
references.citation: Trends Cardiovasc Med. 2001 Jul;11(5):177-84
references.pmid: 11597828
references.citation: Cell Stem Cell. 2007 Oct 11;1(4):428-42
references.pmid: 18371379
references.citation: Development. 1999 Nov;126(22):5073-84
references.pmid: 10529424
references.citation: Development. 2003 Sep;130(18):4393-403
references.pmid: 12900455
references.citation: Nucleic Acids Res. 2003 Mar 1;31(5):e20
references.pmid: 12595569
references.citation: Stem Cells. 2006 Mar;24(3):575-86
references.pmid: 16339996
references.citation: Blood. 2006 Apr 15;107(8):3122-30
references.pmid: 16403910
references.citation: Methods Mol Biol. 2006;330:287-301
references.pmid: 16846032
references.citation: Blood. 2011 May 5;117(18):4924-34
references.pmid: 21263157
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6662-7
references.pmid: 18445648
references.citation: Blood. 2010 Nov 11;116(19):3972-80
references.pmid: 20720183
references.citation: Methods Mol Biol. 2002;185:71-81
references.pmid: 11769014
references.citation: Nat Rev Genet. 2007 May;8(5):368-81
references.pmid: 17387317
references.citation: Cell. 2008 Feb 22;132(4):661-80
references.pmid: 18295582
references.citation: Blood. 2006 Jan 1;107(1):111-7
references.pmid: 16166582
references.citation: Blood. 2007 Jul 15;110(2):509-18
references.pmid: 17403918
references.citation: Blood. 2003 Jan 15;101(2):508-16
references.pmid: 12393529
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13490-5
references.pmid: 16150722
references.citation: Stem Cells. 2010 Jun;28(6):1089-98
references.pmid: 20506544
references.citation: Methods Enzymol. 2003;365:39-59
references.pmid: 14696336
references.citation: Development. 2010 Sep 1;137(17):2829-39
references.pmid: 20659975
references.citation: Exp Hematol. 2012 Oct;40(10):837-46
references.pmid: 22728030