Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells

Publication Date:
2018-05-18
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
Published by:
http://www.hematology.org/
_version_ 1836398932819705857
autor Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
beschreibung Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 inactivation resulted in embryonic lethality with severe anemia at embryonic day 13.5 despite normal emergence of functional HSCs. Ezh2- deficient FL endothelium overexpressed Mmp9, which cell-extrinsically depleted the membrane-bound form of Kit ligand (mKitL), an essential hematopoietic cytokine, in FL. Furthermore, Mmp9 inhibition in vitro restored mKitL expression along with the erythropoiesis supporting capacity of FL endothelial cells. These data establish that Ezh2 is intrinsically dispensable for FL HSCs and provides proof of principle that modulation of epigenetic regulators in niche components can exert a marked cell-extrinsic impact.
citation_standardnr 6260880
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-05-18
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/131/20/2223?rss=1
schlagwort Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
search_space articles
shingle_author_1 Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
shingle_author_2 Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
shingle_author_3 Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
shingle_author_4 Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
shingle_catch_all_1 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 inactivation resulted in embryonic lethality with severe anemia at embryonic day 13.5 despite normal emergence of functional HSCs. Ezh2- deficient FL endothelium overexpressed Mmp9, which cell-extrinsically depleted the membrane-bound form of Kit ligand (mKitL), an essential hematopoietic cytokine, in FL. Furthermore, Mmp9 inhibition in vitro restored mKitL expression along with the erythropoiesis supporting capacity of FL endothelial cells. These data establish that Ezh2 is intrinsically dispensable for FL HSCs and provides proof of principle that modulation of epigenetic regulators in niche components can exert a marked cell-extrinsic impact.
Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 inactivation resulted in embryonic lethality with severe anemia at embryonic day 13.5 despite normal emergence of functional HSCs. Ezh2- deficient FL endothelium overexpressed Mmp9, which cell-extrinsically depleted the membrane-bound form of Kit ligand (mKitL), an essential hematopoietic cytokine, in FL. Furthermore, Mmp9 inhibition in vitro restored mKitL expression along with the erythropoiesis supporting capacity of FL endothelial cells. These data establish that Ezh2 is intrinsically dispensable for FL HSCs and provides proof of principle that modulation of epigenetic regulators in niche components can exert a marked cell-extrinsic impact.
Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 inactivation resulted in embryonic lethality with severe anemia at embryonic day 13.5 despite normal emergence of functional HSCs. Ezh2- deficient FL endothelium overexpressed Mmp9, which cell-extrinsically depleted the membrane-bound form of Kit ligand (mKitL), an essential hematopoietic cytokine, in FL. Furthermore, Mmp9 inhibition in vitro restored mKitL expression along with the erythropoiesis supporting capacity of FL endothelial cells. These data establish that Ezh2 is intrinsically dispensable for FL HSCs and provides proof of principle that modulation of epigenetic regulators in niche components can exert a marked cell-extrinsic impact.
Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
Hematopoiesis and Stem Cells, Red Cells, Iron, and Erythropoiesis
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 inactivation resulted in embryonic lethality with severe anemia at embryonic day 13.5 despite normal emergence of functional HSCs. Ezh2- deficient FL endothelium overexpressed Mmp9, which cell-extrinsically depleted the membrane-bound form of Kit ligand (mKitL), an essential hematopoietic cytokine, in FL. Furthermore, Mmp9 inhibition in vitro restored mKitL expression along with the erythropoiesis supporting capacity of FL endothelial cells. These data establish that Ezh2 is intrinsically dispensable for FL HSCs and provides proof of principle that modulation of epigenetic regulators in niche components can exert a marked cell-extrinsic impact.
Neo, W. H., Booth, C. A. G., Azzoni, E., Chi, L., Delgado-Olguin, P., de Bruijn, M. F. T. R., Jacobsen, S. E. W., Mead, A. J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
shingle_title_2 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
shingle_title_3 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
shingle_title_4 Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
timestamp 2025-06-30T23:34:56.614Z
titel Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
titel_suche Cell-extrinsic hematopoietic impact of Ezh2 inactivation in fetal liver endothelial cells
topic W
WW-YZ
uid ipn_articles_6260880