Fetal stromal niches enhance human embryonic stem cell-derived hematopoietic differentiation and globin switch
| Autor: | Kathy Yuen Yee Chan, Kam Sze Tsang, King Yiu Lee, Benny Shu Pan Fong, Audrey Carmen Lam, Pak Cheung Ng, Chi Chiu Wang, Hsiang-Fu Kung, Tze Kin Lau, Karen Li, Chi Kong Li |
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| Rok vydání: | 2010 |
| Předmět: |
Stromal cell
Stem cell factor Embryoid body beta-Globins Biology Cell Line Colony-Forming Units Assay Mice Fetus medicine Animals Humans Progenitor cell Yolk sac Stem Cell Niche Embryoid Bodies Embryonic Stem Cells Cell Proliferation Cell Differentiation Cell Biology Hematology Embryonic stem cell Cell biology Globins Hematopoiesis Haematopoiesis medicine.anatomical_structure Gene Expression Regulation Culture Media Conditioned embryonic structures Immunology Leukocyte Common Antigens Bone marrow Stromal Cells Developmental Biology |
| Zdroj: | Stem cells and development. 20(1) |
| ISSN: | 1557-8534 |
| Popis: | Hematopoiesis during mammalian embryonic development has been perceived as a migratory phenomenon, from the yolk sac blood island to the aorta-gonad-mesonephros (AGM) region, fetal liver (FL), and subsequently, the fetal bone marrow. In this study, we investigated the effects of primary stromal cells from fetal hematopoietic niches and their conditioned media (CM), applied singly or in sequential orders, on induction of human embryonic stem cells, H1, H9, and H14 lines, to hematopoietic cells. Our results demonstrated that stromal support of FL, AGM + FL, and AGM + FL + fetal bone marrow significantly increased the proliferation of embryoid bodies (EB) at day 18 of hematopoietic induction in the presence of thrombopoietin, stem cell factor, and Flt-3 ligand. AGM + FL also increased hematopoietic colony-forming unit (CFU) formation. CM did not enhance EB proliferation but CM of FL and AGM + FL significantly increased the density of total CFU and early erythroid (burst-forming unit) progenitors. Increased commitment to the hematopoietic lineage was demonstrated by enhanced expressions of CD45, alpha-, beta-, and gamma-globins in CFU at day 32, compared with EB at day 18. CM of FL significantly increased these globin expressions, indicating enhanced switches from embryonic to fetal and adult erythropoiesis. Over 50% and 10% of cells derived from CFU expressed CD45 and beta-globin proteins, respectively. Expressions of hematopoietic regulatory genes (Bmi-1, β-Catenin, Hox B4, GATA-1) were increased in EB or CFU cultures supported by FL or sequential CM. Our study has provided a strategy for derivation of hematopoietic cells from embryonic stem cells under the influence of primary hematopoietic niches and CM, particularly the FL. |
| Databáze: | OpenAIRE |
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