Epo receptor signaling in macrophages alters the splenic niche to promote erythroid differentiation.
Animals
Cell Differentiation
Dinoprostone
/ genetics
Erythroid Cells
/ cytology
Humans
Macrophages
/ cytology
Mice
Mice, Transgenic
PPAR gamma
/ genetics
Prostaglandin D2
/ analogs & derivatives
Receptors, Erythropoietin
/ genetics
STAT5 Transcription Factor
/ genetics
Signal Transduction
Spleen
/ cytology
Stem Cell Niche
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
received:
25
09
2019
accepted:
04
04
2020
pubmed:
1
5
2020
medline:
26
2
2021
entrez:
1
5
2020
Statut:
ppublish
Résumé
Anemic stress induces stress erythropoiesis, which rapidly generates new erythrocytes to restore tissue oxygenation. Stress erythropoiesis is best understood in mice where it is extramedullary and occurs primarily in the spleen. However, both human and mouse stress erythropoiesis use signals and progenitor cells that are distinct from steady-state erythropoiesis. Immature stress erythroid progenitors (SEPs) are derived from short-term hematopoietic stem cells. Although the SEPs are capable of self-renewal, they are erythroid restricted. Inflammation and anemic stress induce the rapid proliferation of SEPs, but they do not differentiate until serum erythropoietin (Epo) levels increase. Here we show that rather than directly regulating SEPs, Epo promotes this transition from proliferation to differentiation by acting on macrophages in the splenic niche. During the proliferative stage, macrophages produce canonical Wnt ligands that promote proliferation and inhibit differentiation. Epo/Stat5-dependent signaling induces the production of bioactive lipid mediators in macrophages. Increased production of prostaglandin J2 (PGJ2) activates peroxisome proliferator-activated receptor γ (PPARγ)-dependent repression of Wnt expression, whereas increased production of prostaglandin E2 (PGE2) promotes the differentiation of SEPs.
Identifiants
pubmed: 32350523
pii: S0006-4971(20)61901-2
doi: 10.1182/blood.2019003480
pmc: PMC7357191
doi:
Substances chimiques
PPAR gamma
0
Pparg protein, mouse
0
Receptors, Erythropoietin
0
STAT5 Transcription Factor
0
9-deoxy-delta-9-prostaglandin D2
60203-57-8
Dinoprostone
K7Q1JQR04M
Prostaglandin D2
RXY07S6CZ2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
235-246Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK077152
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK080040
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119865
Pays : United States
Informations de copyright
© 2020 by The American Society of Hematology.
Références
Blood. 2019 Aug 1;134(5):413-414
pubmed: 31371394
Br J Haematol. 2016 Apr;173(2):206-18
pubmed: 26846448
Curr Top Dev Biol. 2008;82:23-53
pubmed: 18282516
Cell. 2009 Mar 20;136(6):1136-47
pubmed: 19303855
Immunity. 2016 Feb 16;44(2):287-302
pubmed: 26872696
Blood. 2009 Jan 22;113(4):911-8
pubmed: 18927434
Nat Med. 2004 Jan;10(1):55-63
pubmed: 14702635
Cell. 1995 Dec 1;83(5):803-12
pubmed: 8521497
Methods Mol Biol. 2018;1698:91-102
pubmed: 29076085
Blood. 2015 Mar 12;125(11):1803-12
pubmed: 25608563
Transfus Clin Biol. 2010 Sep;17(3):110-1
pubmed: 20655267
Mol Cell Biol. 2004 Sep;24(18):8037-47
pubmed: 15340066
Blood. 2019 Aug 1;134(5):480-491
pubmed: 31101625
Front Immunol. 2017 Sep 20;8:1140
pubmed: 28979259
Development. 2018 Jan 10;145(1):
pubmed: 29321181
Nature. 2007 Feb 8;445(7128):661-5
pubmed: 17251932
Blood Adv. 2019 Jul 23;3(14):2205-2217
pubmed: 31324641
Nat Med. 2012 Mar 04;18(4):572-9
pubmed: 22388089
Cell. 2011 Oct 28;147(3):577-89
pubmed: 22036566
Nat Med. 2013 Apr;19(4):429-36
pubmed: 23502962
J Clin Invest. 2010 Dec;120(12):4507-19
pubmed: 21060151
Science. 2001 Nov 30;294(5548):1871-5
pubmed: 11729303
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20979-84
pubmed: 18077391
Nature. 1999 Apr 1;398(6726):431-6
pubmed: 10201374
Curr Opin Hematol. 2010 Jul;17(4):308-12
pubmed: 20473159
Microbes Infect. 2012 Mar;14(3):238-46
pubmed: 22094132
Biochem J. 2003 Dec 15;376(Pt 3):607-13
pubmed: 12954078
Dev Cell. 2019 Feb 25;48(4):429-444
pubmed: 30782412
Haematologica. 2018 Jan;103(1):40-50
pubmed: 29051279
J Biol Chem. 2000 Jan 21;275(3):1873-7
pubmed: 10636887
Blood. 2008 Aug 1;112(3):470-8
pubmed: 18650462
Front Immunol. 2018 Apr 13;9:745
pubmed: 29706964
Curr Opin Hematol. 2011 May;18(3):139-45
pubmed: 21372709
Blood. 2005 Apr 1;105(7):2741-8
pubmed: 15591122
Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):3-9
pubmed: 21722751
BMC Cancer. 2005 Jan 10;5:3
pubmed: 15642117
Nature. 1996 Aug 15;382(6592):638-42
pubmed: 8757136
Biochem Biophys Res Commun. 2000 Nov 30;278(3):704-11
pubmed: 11095972
Nat Med. 2013 Apr;19(4):437-45
pubmed: 23502961
Leuk Res. 1989;13(7):527-34
pubmed: 2788237
Development. 2001 Apr;128(8):1253-64
pubmed: 11262227
J Biol Chem. 2005 Apr 8;280(14):14145-53
pubmed: 15695504
Blood. 2018 Dec 13;132(24):2580-2593
pubmed: 30322871
Jpn J Pharmacol. 1998 Sep;78(1):11-22
pubmed: 9804057
Sci Signal. 2019 Sep 10;12(598):
pubmed: 31506384
Immunity. 2011 Jan 28;34(1):61-74
pubmed: 21256055
Blood. 2007 May 15;109(10):4494-502
pubmed: 17284534
Rev Hematol. 1958 Jan-Mar;13(1):8-11
pubmed: 13555228