Endothelial MEKK3-KLF2/4 signaling integrates inflammatory and hemodynamic signals during definitive hematopoiesis.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
12 05 2022
12 05 2022
Historique:
received:
01
09
2021
accepted:
11
02
2022
pubmed:
5
3
2022
medline:
18
5
2022
entrez:
4
3
2022
Statut:
ppublish
Résumé
The hematopoietic stem cells (HSCs) that produce blood for the lifetime of an animal arise from RUNX1+ hemogenic endothelial cells (HECs) in the embryonic vasculature through a process of endothelial-to-hematopoietic transition (EHT). Studies have identified inflammatory mediators and fluid shear forces as critical environmental stimuli for EHT, raising the question of how such diverse inputs are integrated to drive HEC specification. Endothelial cell MEKK3-KLF2/4 signaling can be activated by both fluid shear forces and inflammatory mediators, and it plays roles in cardiovascular development and disease that have been linked to both stimuli. Here we demonstrate that MEKK3 and KLF2/4 are required in endothelial cells for the specification of RUNX1+ HECs in both the yolk sac and dorsal aorta of the mouse embryo and for their transition to intraaortic hematopoietic cluster (IAHC) cells. The inflammatory mediators lipopolysaccharide and interferon-γ increase RUNX1+ HECs in an MEKK3-dependent manner. Maternal administration of catecholamines that stimulate embryo cardiac function and accelerate yolk sac vascular remodeling increases EHT by wild-type but not MEKK3-deficient endothelium. These findings identify MEKK-KLF2/4 signaling as an essential pathway for EHT and provide a molecular basis for the integration of diverse environmental inputs, such as inflammatory mediators and hemodynamic forces, during definitive hematopoiesis.
Identifiants
pubmed: 35245372
pii: S0006-4971(22)00321-4
doi: 10.1182/blood.2021013934
pmc: PMC9101247
doi:
Substances chimiques
Core Binding Factor Alpha 2 Subunit
0
Inflammation Mediators
0
Klf2 protein, mouse
0
Kruppel-Like Transcription Factors
0
MAP Kinase Kinase Kinase 3
EC 2.7.11.25
MAP3K3 protein, human
EC 2.7.11.25
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2942-2957Subventions
Organisme : NIDDK NIH HHS
ID : T32 DK007780
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007439
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL091724
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD089245
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142976
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG066905
Pays : United States
Informations de copyright
© 2022 by The American Society of Hematology.
Références
Genes Dev. 2014 Dec 1;28(23):2597-612
pubmed: 25395663
Methods Mol Biol. 2018;1698:117-132
pubmed: 29076087
Dev Cell. 2020 Feb 24;52(4):446-460.e5
pubmed: 32032546
J Biol Chem. 2003 Sep 26;278(39):36989-92
pubmed: 12912994
Cell. 1996 Sep 20;86(6):897-906
pubmed: 8808625
PLoS Biol. 2009 Nov;7(11):e1000246
pubmed: 19924233
Nature. 2016 Apr 7;532(7597):122-6
pubmed: 27027284
Development. 1999 Jun;126(11):2563-75
pubmed: 10226014
Immunol Rev. 2006 Feb;209:95-102
pubmed: 16448536
Mech Dev. 2007 Sep-Oct;124(9-10):762-74
pubmed: 17709232
Curr Biol. 2015 May 18;25(10):1354-61
pubmed: 25959969
Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2069-77
pubmed: 12574001
Nature. 2017 May 25;545(7655):439-445
pubmed: 28514438
Dev Cell. 2017 Nov 6;43(3):274-289.e5
pubmed: 29056552
Cell Rep. 2016 Nov 22;17(9):2286-2298
pubmed: 27880904
PLoS One. 2013;8(2):e54891
pubmed: 23457456
Blood. 2002 Sep 1;100(5):1689-98
pubmed: 12176889
Nat Biotechnol. 2020 Dec;38(12):1408-1414
pubmed: 32747759
Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1468-73
pubmed: 21209332
PLoS One. 2015 Apr 01;10(4):e0122622
pubmed: 25830332
Stem Cells. 2016 Feb;34(2):431-44
pubmed: 26418893
Nature. 1995 Apr 13;374(6523):640-3
pubmed: 7715703
Am J Physiol Cell Physiol. 2007 Oct;293(4):C1404-11
pubmed: 17687003
Genesis. 2010 Sep;48(9):563-7
pubmed: 20645309
Dev Cell. 2014 Dec 8;31(5):640-53
pubmed: 25490269
Nature. 2017 May 18;545(7654):305-310
pubmed: 28489816
Curr Top Dev Biol. 2017;124:125-160
pubmed: 28335858
Exp Hematol. 2018 Apr;60:1-9
pubmed: 29287940
J Immunol. 2011 May 15;186(10):5791-800
pubmed: 21471448
Development. 2007 Sep;134(18):3317-26
pubmed: 17720695
Development. 2013 Oct;140(19):4041-50
pubmed: 24004946
EMBO J. 2000 Jun 1;19(11):2465-74
pubmed: 10835345
J Clin Invest. 2006 Jan;116(1):49-58
pubmed: 16341264
Cell. 2009 May 15;137(4):736-48
pubmed: 19450519
J Biol Chem. 1999 Dec 17;274(51):36035-8
pubmed: 10593883
Int J Dev Biol. 2010;54(6-7):1011-8
pubmed: 20711979
Am J Pathol. 2005 Aug;167(2):609-18
pubmed: 16049344
Blood. 2005 Oct 1;106(7):2566-71
pubmed: 15947087
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
Dev Cell. 2006 Dec;11(6):845-57
pubmed: 17141159
Microcirculation. 2011 Feb;18(2):102-17
pubmed: 21166929
Nature. 1995 Apr 13;374(6523):643-6
pubmed: 7715704
Stem Cells. 2012 Aug;30(8):1611-23
pubmed: 22628281
Nat Immunol. 2004 Jan;5(1):98-103
pubmed: 14661019
Am J Pathol. 2008 Apr;172(4):1088-99
pubmed: 18292233
Sci Rep. 2017 Mar 08;7:43817
pubmed: 28272478
J Biol Chem. 2006 Jun 2;281(22):15121-8
pubmed: 16571724
Blood. 2008 Apr 1;111(7):3435-8
pubmed: 17932251
Nature. 2009 Jun 25;459(7250):1131-5
pubmed: 19440194
Blood. 2016 Jul 14;128(2):204-16
pubmed: 27095787
Nat Genet. 2000 Mar;24(3):309-13
pubmed: 10700190
Blood. 2008 Dec 15;112(13):4895-904
pubmed: 18805969
Blood. 2011 Oct 13;118(15):4102-10
pubmed: 21849483
Nat Commun. 2020 Jan 29;11(1):586
pubmed: 31996681
Cell Res. 2020 May;30(5):376-392
pubmed: 32203131
Cell Stem Cell. 2013 Nov 7;13(5):535-48
pubmed: 24054998
Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14284-9
pubmed: 26540726
J Exp Med. 2015 Sep 21;212(10):1571-87
pubmed: 26347473
Cell. 2014 Nov 20;159(5):1070-1085
pubmed: 25416946
Dev Dyn. 2016 Oct;245(10):1011-28
pubmed: 27389484
Biochem Biophys Res Commun. 2006 Mar 24;341(4):1244-51
pubmed: 16466697
Blood. 2020 Aug 13;136(7):845-856
pubmed: 32392346
J Exp Med. 2004 May 17;199(10):1305-15
pubmed: 15136591
Blood. 2007 Nov 1;110(9):3417-25
pubmed: 17675555
Development. 2015 Aug 1;142(15):2719-24
pubmed: 26243871
Blood. 2015 Feb 12;125(7):1098-106
pubmed: 25540193
Biochem Biophys Res Commun. 2010 Jan 1;391(1):984-9
pubmed: 19968965
Circ Res. 2005 Jun 24;96(12):1291-8
pubmed: 15920020
Annu Rev Physiol. 2021 Feb 10;83:17-37
pubmed: 33035429
Dev Cell. 2015 Jan 26;32(2):168-80
pubmed: 25625206
JCI Insight. 2017 Feb 23;2(4):e91700
pubmed: 28239661
Nat Commun. 2015 Aug 03;6:7937
pubmed: 26235885
Circ Res. 2003 Feb 7;92(2):133-5
pubmed: 12574139
Biol Chem. 2004 Aug;385(8):723-9
pubmed: 15449708
Front Immunol. 2016 Nov 07;7:487
pubmed: 27872627
Genes Dev. 2020 Jul 1;34(13-14):950-964
pubmed: 32499402
Development. 2004 Jan;131(2):361-75
pubmed: 14681188
Genes Dev. 2016 Jun 15;30(12):1454-69
pubmed: 27313318
BMC Dev Biol. 2013 Nov 22;13:40
pubmed: 24261709