Noncanonical Wnt signaling orchestrates early developmental events toward hematopoietic cell fate from human embryonic stem cells.
During 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.
Vijayaragavan
Kausalia
K
Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Szabo
Eva
E
Bossé
Marc
M
Ramos-Mejia
Veronica
V
Moon
Randall T
RT
Bhatia
Mickie
M
D019521:Body Patterning; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism* / Q000494:pharmacology; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D015820:Cadherins; D017077:Culture Media, Conditioned; C115810:FZD7 protein, human; D051157:Frizzled Receptors; D043562:Receptors, G-Protein-Coupled; C555510:WNT3A protein, human; D051153:Wnt Proteins; C540523:Wnt11 protein, human; D060508:Wnt3 Protein; D060509:Wnt3A Protein