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

Author

Listed:
  • Shunsuke Mori

    (Kyoto University
    Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology
    Rutgers, The State University of New Jersey)

  • Eriko Sakakura

    (Kyoto University)

  • Yuji Tsunekawa

    (Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology)

  • Masaya Hagiwara

    (Osaka Prefecture University)

  • Takayuki Suzuki

    (Nagoya University)

  • Mototsugu Eiraku

    (Kyoto University
    Laboratory for in vitro Histogenesis, RIKEN Center for Developmental Biology
    Kyoto University, Yoshida-Konoe-cho)

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.

Suggested Citation

  • Shunsuke Mori & Eriko Sakakura & Yuji Tsunekawa & Masaya Hagiwara & Takayuki Suzuki & Mototsugu Eiraku, 2019. "Self-organized formation of developing appendages from murine pluripotent stem cells," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11702-y
    DOI: 10.1038/s41467-019-11702-y
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