Generation of a limb-like organoid by taking advantage of direct reprogramming and 3D-culture techniques

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22658
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Atsuta Yuji 九州大学, 理学研究院, 助教 (80874685)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 四肢前駆細胞 / ダイレクトリプログラミング / オルガノイド

Outline of Final Research Achievements

The limb bud consists of mesenchymal progenitors derived from the lateral plate mesoderm (LPM) that produce most of the tissues of the mature limb. The LPM also gives rise to the mesodermal components of the flank and neck. However, the mesenchymal cells generated at these other axial levels cannot produce the variety of cell types found in the limb bud, even when exposed to signals responsible for organizing the limb bud. By taking advantage of a reprogramming approach, we find a set of factors (Prdm16, Zbtb16 and Lin28) that are capable of imparting limb progenitor-like properties to non-limb fibroblasts. The reprogrammed cells show similar gene expression profiles, and can differentiate into similar cell types, as endogenous limb progenitors. The further addition of Lin41 potentiates proliferation of the reprogrammed cells while suppressing differentiation. These results suggest that these same four key factors may play pivotal roles in the formation of endogenous limb progenitors.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で見出された成果は、四肢形成開始のメカニズムの理解を深めるとともに、四肢再生医療の発展へと寄与することが期待される。
（1）四肢形成の理解;見出されたリプログラム因子は、四肢形成過程の最初期段階である、四肢前駆細胞の特定化においても中心的な役割を果たすことが考えられる。
（2）四肢再生医療への応用;本研究成果により手足以外の細胞から直接、LP細胞を作製できることが示唆された。誘導されたリプログラム細胞は細胞治療へと活用できる可能性がある。