Neuronal differentiation of MUSE cells mediated by neuronal differentiation control peptides and application to neuronal regeneration medicine

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10366
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: International University of Health and Welfare (2016-2018); Yokohama City University (2015)
• Principal Investigator: Kanno Hiroshi 国際医療福祉大学, 医学部, 教授 (40244496)
• Co-Investigator(Kenkyū-buntansha): 宮川 拓也 東京大学, 大学院農学生命科学研究科(農学部), 特任准教授 (50596559) ; 田之倉 優 東京大学, 大学院農学生命科学研究科(農学部), 特任教授 (60136786)
• Research Collaborator: Dezawa Mari
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: MUSE細胞 / 幹細胞 / 神経分化誘導 / BCボックスモチーフ / 再生医療

Outline of Final Research Achievements

MUSE cells were sorted from skin-derived precursors with the MACS method. Neuronal differentiation of MUSE cells was induced by intracellular delivery of a VHL peptide composed of the BC-box motif [(A,P,S,T)LXXX (A,C) XXX(A,I,L,V)] corresponding to binding site of elongin BC. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by JAK2 ubiquitination of JAK2 and inhibition of the JAK2/STAT3 pathway. Then, we showed that different NDD peptide-delivered cells differentiated into different kinds of neuron-like cells. That is, dopaminergic neuron-like cells, cholinergic neuron-like cells, GABAnergic neuron-like cells or rhodopsin-positive neuron-like cells were induced by different NDD peptides. These novel findings might contribute to the development of a new method for promoting neuronal differentiation and shed further light on the mechanism of neuronal differentiation of somatic stem cells.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

MUSE細胞は多能性組織幹細胞であり, iPS細胞と同様な多分化能を有するが, iPS細胞のような癌形成能はなく安全であり,再生医療のドナー細胞として期待される。MUSE細胞は無処理のまま静脈内へ投与しても組織を修復する機能を有するが, 目的の細胞へ分化誘導後に投与した方が効率よく組織を修復する。ここではBCボックスモチーフ由来の神経分化誘導ペプチドを用いて, MUSE細胞から種々の神経細胞へ分化させる方法を提示し, かつ神経分化転写経路の一部を解明することに成功した。このことは,他の幹細胞にも応用ができる可能性が高く， 幹細胞を用いた神経再生医療を改良を加えた点で社会的意義も大きい。