Self-organized formation of developing appendages from murine pluripotent stem cells
Shunsuke Mori1,2,3, Eriko Sakakura4, Yuji Tsunekawa5
1Laboratory of Developmental Systems, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan. shunsuke.mori@rutgers.edu.
Nature Communications
|August 25, 2019
Summary
Scientists induced limb bud-like tissues from pluripotent stem cells (PSCs) in vitro. These engineered tissues mimic natural limb development and can integrate with existing tissues after transplantation.
Area of Science:
- Developmental biology
- Stem cell biology
- Regenerative medicine
Background:
- Limb development involves complex interactions between mesenchyme and epithelium derived from different germ layers.
- Understanding limb bud formation is crucial for regenerative approaches to limb defects.
Purpose of the Study:
- To develop an in vitro method for generating limb bud-like mesenchymal/epithelial complex tissues from pluripotent stem cells (PSCs).
- To investigate the potential of these engineered tissues to mimic early limb development and contribute to digit formation.
Main Methods:
- Induction of limb bud-like tissues from murine PSCs using specific culture conditions.
- Retinoic acid concentration gradients to direct forelimb/hindlimb mesenchyme differentiation.
- Bone morphogenetic protein (BMP) signaling manipulation to induce apical ectodermal ridge-like structures.
- Comparative transcriptome analysis to assess gene expression similarity with endogenous limb buds.
- In vivo transplantation experiments to evaluate tissue integration and contribution to digit formation.
Main Results:
- Successfully generated LB-like mesenchymal/epithelial complex tissues from PSCs in vitro.
- Demonstrated selective differentiation into forelimb or hindlimb mesenchyme based on retinoic acid concentration.
- Transcriptome analysis revealed gene expression patterns similar to endogenous limb buds.
- Induced apical ectodermal ridge-like structures by manipulating BMP signaling.
- Showed that induced tissues can contribute to endogenous digit formation after transplantation.
Conclusions:
- Developed a novel PSC-based technology for creating artificial limb buds in culture.
- This method provides a valuable platform for studying limb development and potentially for regenerative therapies.
- The technology may be applicable to inducing other complex mesenchymal/epithelial tissues from PSCs.
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