1. Noncanonical Wnt Signaling Orchestrates Early Developmental Events toward Hematopoietic Cell Fate from Human Embryonic Stem Cells
- Author
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Eva Szabo, Mickie Bhatia, Kausalia Vijayaragavan, Randall T. Moon, Marc Bossé, and Verónica Ramos-Mejía
- Subjects
Brachyury ,Mesoderm ,animal structures ,Embryoid body ,Cell fate determination ,Biology ,Article ,Cell Line ,Receptors, G-Protein-Coupled ,Wnt3 Protein ,03 medical and health sciences ,0302 clinical medicine ,Wnt3A Protein ,medicine ,Genetics ,Humans ,natural sciences ,Embryonic Stem Cells ,Body Patterning ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,Wnt signaling pathway ,Cell Biology ,Cadherins ,STEMCELL ,Embryonic stem cell ,Frizzled Receptors ,Hematopoiesis ,Cell biology ,Wnt Proteins ,medicine.anatomical_structure ,Culture Media, Conditioned ,030220 oncology & carcinogenesis ,embryonic structures ,Molecular Medicine ,Stem cell ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
SummaryDuring human development, signals that govern lineage specification versus expansion of cells committed to a cell fate are poorly understood. We demonstrate that activation of canonical Wnt signaling by Wnt3a promotes proliferation of human embryonic stem cells (hESCs)—precursors already committed to the hematopoietic lineage. In contrast, noncanonical Wnt signals, activated by Wnt11, control exit from the pluripotent state and entry toward mesoderm specification. Unique to embryoid body (EB) formation of hESCs, Wnt11 induces development and arrangement of cells expressing Brachyury that coexpress E-cadherin and Frizzled-7 (Fzd7). Knockdown of Fzd7 expression blocks Wnt11-dependent specification. Our study reveals an unappreciated role for noncanonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs.
- Published
- 2009
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