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Self-organized formation of developing appendages from murine pluripotent stem cells

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11702-y

2041-1723

Shunsuke Mori, Eriko Sakakura, Yuji Tsunekawa, Masaya HAGIWARA, Takayuki Suzuki, Mototsugu Eiraku,

Tissue Engineering and Regenerative Medicine

Abstract Limb development starts with the formation of limb buds (LBs), which consist of tissues from two different germ layers; the lateral plate mesoderm-derived mesenchyme and ectoderm-derived surface epithelium. Here, we report means for induction of an LB-like mesenchymal/epithelial complex tissues from murine pluripotent stem cells (PSCs) in vitro. The LB-like tissues selectively differentiate into forelimb- or hindlimb-type mesenchymes, depending on a concentration of retinoic acid. Comparative transcriptome analysis reveals that the LB-like tissues show similar gene expression pattern to that seen in LBs. We also show that manipulating BMP signaling enables us to induce a thickened epithelial structure similar to the apical ectodermal ridge. Finally, we demonstrate that the induced tissues can contribute to endogenous digit tissue after transplantation. This PSC technology offers a first step for creating an artificial limb bud in culture and might open the door to inducing other mesenchymal/epithelial complex tissues from PSCs.