Il Ho Jang

Research Interests:

We have explored the role of Notch1 signaling in hematopoietic development using mouse and human embryoid bodies (EBs). We induced ICN1 transiently from day 3 to 5 of EB development, and detected a significant increase in hematopoietic colony formation in methylcellulose and on OP9 stroma. When we dissociated day 3 EBs and assayed for the hemangioblast (BL-CFC), we noted a marked decrease of BL-CFCs in response to Notch induction. RT-PCR analysis of Notch-induced BL-CFCs revealed up-regulation of hematopoietic genes (b-H1 and more significantly b-Major) but no difference in endothelial gene expression (Flk1 and Tie2). Re-plating of Notch-induced blast colonies failed to show a skewing toward hematopoietic fates, suggesting that Notch1 signaling does not appear to promote hematopoietic fate at the level of the hemangioblast. Instead, we noted that ICN1 induction from day 3-5 of EB development caused an increase in the VE-cadherin+ population of putative hemogenic endothelial progenitors. Plating of the VE-cadherin+CD41-CD45- population into media containing VEGF and hematopoietic cytokines results in the formation of an endothelial layer with semi-adherent hematopoietic cells on top. When Notch was induced during EB development, we observed a dramatic increase in hematopoietic outgrowth from VE-cadherin+CD41-CD45- cells. We explored the effect of addition of Notch1 ligand, Dll4 during formation of EBs from human ES cells, and noted a marked increase in definitive methycellulose colonies, especially CFU-GEMM, and a switch from embryonic (e) to fetal type (g) globin gene expression. Our observations implicate Notch1 signaling in promoting the formation of hematopoietic progenitors from hemogenic endothelial cells.



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		Il-Ho Jang, B.S. BBS Program, Harvard Medical School Doctoral Candidate
		Research Interests: We have explored the role of Notch1 signaling in hematopoietic development using mouse and human embryoid bodies (EBs). We induced ICN1 transiently from day 3 to 5 of EB development, and detected a significant increase in hematopoietic colony formation in methylcellulose and on OP9 stroma. When we dissociated day 3 EBs and assayed for the hemangioblast (BL-CFC), we noted a marked decrease of BL-CFCs in response to Notch induction. RT-PCR analysis of Notch-induced BL-CFCs revealed up-regulation of hematopoietic genes (b-H1 and more significantly b-Major) but no difference in endothelial gene expression (Flk1 and Tie2). Re-plating of Notch-induced blast colonies failed to show a skewing toward hematopoietic fates, suggesting that Notch1 signaling does not appear to promote hematopoietic fate at the level of the hemangioblast. Instead, we noted that ICN1 induction from day 3-5 of EB development caused an increase in the VE-cadherin+ population of putative hemogenic endothelial progenitors. Plating of the VE-cadherin+CD41-CD45- population into media containing VEGF and hematopoietic cytokines results in the formation of an endothelial layer with semi-adherent hematopoietic cells on top. When Notch was induced during EB development, we observed a dramatic increase in hematopoietic outgrowth from VE-cadherin+CD41-CD45- cells. We explored the effect of addition of Notch1 ligand, Dll4 during formation of EBs from human ES cells, and noted a marked increase in definitive methycellulose colonies, especially CFU-GEMM, and a switch from embryonic (e) to fetal type (g) globin gene expression. Our observations implicate Notch1 signaling in promoting the formation of hematopoietic progenitors from hemogenic endothelial cells.
Articles in PubMed