Non-canonical Wnt signaling orchestrates early developmental events towards mesodermal hematopoietic cell fate from human embryonic stem cells

Abstract

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 Wnt-3a promotes proliferation of human embryonic stem cells (hESCs) -precursors already committed to the hematopoietic lineage. In contrast, non-canonical Wnt signals, activated by Wnt11, control exit from the pluripotent state and entry towards mesoderm specification. Unique to embryoid body (EB) formation of hESCs, Wnt11 induces development and arrangement of cells expressing Brachyury that co-express E-cadherin and Frizzled-7 (Fzd7). Knockdown of Fzd7 expression blocks Wnt-11 dependent specification. Our study reveals an unappreciated role for non-canonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs.