The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate

Leukemia
Veronica AyllonPablo Menendez

Abstract

Notch signaling is essential for definitive hematopoiesis, but its role in human embryonic hematopoiesis is largely unknown. We show that in hESCs the expression of the Notch ligand DLL4 is induced during hematopoietic differentiation. We found that DLL4 is only expressed in a sub-population of bipotent hematoendothelial progenitors (HEPs) and segregates their hematopoietic versus endothelial potential. We demonstrate at the clonal level and through transcriptome analyses that DLL4(high) HEPs are enriched in endothelial potential, whereas DLL4(low/-) HEPs are committed to the hematopoietic lineage, albeit both populations still contain bipotent cells. Moreover, DLL4 stimulation enhances hematopoietic differentiation of HEPs and increases the amount of clonogenic hematopoietic progenitors. Confocal microscopy analysis of whole differentiating embryoid bodies revealed that DLL4(high) HEPs are located close to DLL4(low/-) HEPs, and at the base of clusters of CD45+ cells, resembling intra-aortic hematopoietic clusters found in mouse embryos. We propose a model for human embryonic hematopoiesis in which DLL4(low/-) cells within hemogenic endothelium receive Notch-activating signals from DLL4(high) cells, resulting in an endothelial-...Continue Reading

References

Jun 8, 2002·Biochemical and Biophysical Research Communications·Souichi SuenobuToshio Suda
Oct 7, 2004·Genes & Development·António DuarteJanet Rossant
May 21, 2005·The International Journal of Developmental Biology·Manuela Tavian, Bruno Péault
Nov 15, 2006·Cell Biology and Toxicology·D KarlovicM Osmak
Oct 1, 2008·The Journal of Experimental Medicine·Katsuto HozumiSonoko Habu
Dec 2, 2008·Cell Stem Cell·Ann C ZoveinM Luisa Iruela-Arispe
Feb 16, 2010·Nature·Jean-Charles BoissetCatherine Robin
Mar 11, 2010·Current Stem Cell Research & Therapy·Mohammad Saiful IslamDan S Kaufman
Apr 21, 2010·The Journal of Cell Biology·Kohei YamamizuJun K Yamashita
Aug 26, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Veronica Ramos-MejiaPablo Menendez
Dec 1, 2010·Cells, Tissues, Organs·Isabel AlcobiaAntónio Cidadão
Jun 1, 2011·The Journal of Experimental Medicine·Stanislav RybtsovAlexander Medvinsky
Jul 28, 2011·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Diana C ChongOndine Cleaver
Mar 1, 2012·Trends in Immunology·Guilherme CostaGeorges Lacaud
Apr 12, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Pedro J RealPablo Menendez
May 19, 2012·Regenerative Medicine·Thomas Clapes, Catherine Robin
Jul 18, 2012·The Journal of Experimental Medicine·Cristina Ruiz-HerguidoAnna Bigas
Nov 6, 2012·Cell Stem Cell·Shannon McKinney-FreemanGeorge Q Daley
Dec 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Peter Geon KimGeorge Q Daley
Dec 26, 2012·The Journal of Experimental Medicine·Jordi GuiuAnna Bigas

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Citations

Feb 6, 2016·Cellular and Molecular Life Sciences : CMLS·Emily Gritz, Karen K Hirschi
Mar 26, 2016·Annals of the New York Academy of Sciences·Dirk KanzClaudia Lengerke
Sep 7, 2016·FEBS Letters·Emmanuelle JulienManuela Tavian
Jun 3, 2016·Scientific Reports·Inn-Inn ChenGiovanna Tosato
Jan 13, 2018·Frontiers in Immunology·Lidia FrejoJose A Lopez-Escamez
Nov 4, 2016·The EMBO Journal·Martina KonantzClaudia Lengerke
Oct 1, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Hilda Lomelí, Francisco Castillo-Castellanos
May 22, 2018·The Journal of Clinical Investigation·Marina García-PeydróMaría L Toribio
Nov 5, 2019·Journal of Experimental & Clinical Cancer Research : CR·Elisabeth SilkenstedtDolors Colomer
Oct 10, 2020·Annual Review of Physiology·Yinyu Wu, Karen K Hirschi
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Francisco Gutierrez-AgüeraPablo Menendez

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