title: Endothelio-mesenchymal interaction controls runx1 expression and modulates the notch pathway to initiate aortic hematopoiesis.
abstract: Hematopoietic stem cells (HSCs) are produced by a small cohort of hemogenic endothelial cells (ECs) during development through the formation of intra-aortic hematopoietic cell (HC) clusters. The Runx1 transcription factor plays a key role in the EC-to-HC and -HSC transition. We show that Runx1 expression in hemogenic ECs and the subsequent initiation of HC formation are tightly controlled by the subaortic mesenchyme, although the mesenchyme is not a source of HCs. Runx1 and Notch signaling are involved in this process, with Notch signaling decreasing with time in HCs. Inhibiting Notch signaling readily increases HC production in mouse and chicken embryos. In the mouse, however, this increase is transient. Collectively, we show complementary roles of hemogenic ECs and mesenchymal compartments in triggering aortic hematopoiesis. The subaortic mesenchyme induces Runx1 expression in hemogenic-primed ECs and collaborates with Notch dynamics to control aortic hematopoiesis.
authors.affiliation: CNRS, UPMC, UMR7622, Bat C, 6(ème) étage, Case 24, 75252 Paris Cedex 05, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Richard
authors.forename: Cécile
authors.initials: C
authors.lastname: Drevon
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Canto
authors.forename: Gaelle
authors.initials: G
authors.lastname: Villain
authors.forename: Karine
authors.initials: K
authors.lastname: Bollérot
authors.forename: Aveline
authors.initials: A
authors.lastname: Lempereur
authors.forename: Marie-Aimée
authors.initials: MA
authors.lastname: Teillet
authors.forename: Christine
authors.initials: C
authors.lastname: Vincent
authors.forename: Catalina
authors.initials: C
authors.lastname: Rosselló Castillo
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
authors.forename: Eileen
authors.initials: E
authors.lastname: Piwarzyk
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Speck
authors.forename: Michèle
authors.initials: M
authors.lastname: Souyri
authors.forename: Thierry
authors.initials: T
authors.lastname: Jaffredo
mesh_terms: D000818:Animals; D001011:Aorta / Q000254:growth & development / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D002478:Cells, Cultured; D002645:Chickens; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055018:Hemangioblasts; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011784:Quail; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D036341:Intercellular Signaling Peptides and Proteins; C490503:Jag2 protein, mouse; D000072101:Jagged-2 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; C493726:Runx1 protein, mouse; D000072099:Serrate-Jagged Proteins
references.citation: Cell Tissue Res. 1997 May;288(2):207-23
references.pmid: 9082957
references.citation: Development. 2005 Mar;132(5):1117-26
references.pmid: 15689374
references.citation: Cell Stem Cell. 2008 Dec 4;3(6):625-36
references.pmid: 19041779
references.citation: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9399-403
references.pmid: 17517650
references.citation: Blood. 2007 Dec 15;110(13):4188-97
references.pmid: 17823307
references.citation: Dev Cell. 2009 Jun;16(6):909-16
references.pmid: 19531361
references.citation: Mol Cell Biol. 1994 Jan;14(1):473-83
references.pmid: 8264615
references.citation: Blood. 2000 Aug 15;96(4):1591-3
references.pmid: 10942412
references.citation: Nature. 2010 Mar 4;464(7285):112-5
references.pmid: 20154732
references.citation: Development. 1999 Jun;126(11):2563-75
references.pmid: 10226014
references.citation: Blood. 2010 Apr 8;115(14):2777-83
references.pmid: 20107232
references.citation: Dev Dyn. 2009 Mar;238(3):624-31
references.pmid: 19235723
references.citation: Blood. 2009 May 21;113(21):5121-4
references.pmid: 19321859
references.citation: Gene Expr Patterns. 2005 Dec;6(1):29-39
references.pmid: 16033710
references.citation: Dev Dyn. 2001 Mar;220(3):284-9
references.pmid: 11241836
references.citation: Blood. 2010 Sep 23;116(12):2046-56
references.pmid: 20511544
references.citation: Dev Cell. 2008 Jun;14(6):890-901
references.pmid: 18539117
references.citation: Development. 1996 May;122(5):1363-71
references.pmid: 8625825
references.citation: Development. 2009 Aug;136(15):2613-21
references.pmid: 19570846
references.citation: Blood. 2002 Feb 15;99(4):1183-9
references.pmid: 11830464
references.citation: Nature. 2010 Mar 4;464(7285):108-11
references.pmid: 20154733
references.citation: Development. 2008 May;135(10):1823-32
references.pmid: 18417617
references.citation: Dev Biol. 2006 Jan 15;289(2):283-95
references.pmid: 16337933
references.citation: Immunity. 2002 May;16(5):661-72
references.pmid: 12049718
references.citation: Development. 1998 Nov;125(22):4575-83
references.pmid: 9778515
references.citation: EMBO J. 2000 Jun 1;19(11):2465-74
references.pmid: 10835345
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20838-43
references.pmid: 18087045
references.citation: Int J Dev Biol. 2005;49(2-3):269-77
references.pmid: 15906241
references.citation: Nature. 2009 Feb 12;457(7231):887-91
references.pmid: 19129762
references.citation: Blood. 2010 Aug 12;116(6):909-14
references.pmid: 20453160
references.citation: Nature. 2010 Mar 4;464(7285):116-20
references.pmid: 20154729
references.citation: Blood. 2004 Nov 15;104(10):3097-105
references.pmid: 15251982
references.citation: Science. 1994 Aug 19;265(5175):1098-101
references.pmid: 8066449
references.citation: Development. 2010 Nov;137(21):3651-61
references.pmid: 20876651
references.citation: J Exp Med. 2011 Jun 6;208(6):1305-15
references.pmid: 21624936
references.citation: EMBO J. 2008 Jul 9;27(13):1886-95
references.pmid: 18528438
references.citation: Development. 1999 Feb;126(4):617-27
references.pmid: 9895310
references.citation: Nature. 2009 Feb 12;457(7231):892-5
references.pmid: 19182774
references.citation: Dev Biol. 2005 Oct 1;286(1):311-25
references.pmid: 16153632
references.citation: Stem Cells. 2010 Oct;28(10):1869-81
references.pmid: 20799333
references.citation: Genes Dev. 2005 Oct 1;19(19):2331-42
references.pmid: 16166372
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):134-9
references.pmid: 15623562
references.citation: Development. 2006 Mar;133(6):1013-22
references.pmid: 16467362
references.citation: Trends Cardiovasc Med. 2006 May;16(4):128-39
references.pmid: 16713536
references.citation: Blood. 1993 Jul 1;82(1):66-76
references.pmid: 8324235
references.citation: Development. 2002 Sep;129(17):4147-57
references.pmid: 12163416
references.citation: Gene Expr Patterns. 2003 Jun;3(3):261-72
references.pmid: 12799070
references.citation: Mech Dev. 1999 May;83(1-2):161-4
references.pmid: 10381576
references.citation: Blood. 2004 Apr 1;103(7):2522-9
references.pmid: 14630789
references.citation: Development. 2007 Aug;134(16):3031-40
references.pmid: 17634189
references.citation: Dev Dyn. 1999 Jun;215(2):139-47
references.pmid: 10373018
references.citation: Int J Dev Biol. 2010;54(6-7):1045-54
references.pmid: 20711981
references.citation: Nat Immunol. 2008 Feb;9(2):129-36
references.pmid: 18204427
references.citation: Nat Genet. 2008 Jan;40(1):51-60
references.pmid: 17994017
references.citation: Dev Biol. 2005 Apr 15;280(2):307-20
references.pmid: 15882575
references.citation: Dev Dyn. 2010 Jun;239(6):1748-54
references.pmid: 20503370
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17692-7
references.pmid: 17962413
references.citation: Immunity. 2003 May;18(5):699-711
references.pmid: 12753746
references.citation: Nature. 2011 Jun 08;474(7350):220-4
references.pmid: 21654806
references.citation: Nature. 2009 Feb 12;457(7231):896-900
references.pmid: 19212410