Characterization of distal airway stem-like cells expressing N-terminally truncated p63 and thyroid transcription factor-1 in the human lung

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16053
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: Tanaka Yusuke 札幌医科大学, 医学部, 研究員 (70792125)
• Research Collaborator: HIRAI sachie ; YAMAGUCHI miki ; SUMI toshiyuki ; TADA makoto ; SAITO atsushi ; CHIBA hirofumi ; KOJIMA takashi ; WATANABE atsushi ; TAKAHASHI hiroki ; SAKUMA yuji
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: Distal airway stem cell / 末梢肺上皮幹細胞 / TTF-1 / delta Np63 / 3次元培養

Outline of Final Research Achievements

We found that human lung epithelial (HuL) cells, derived from normal, peripheral lung tissue, in monolayer, mostly express both the N-terminally truncated isoform of p63 (delta Np63), a marker for airway basal cells, and thyroid transcription factor-1 (TTF-1), a marker for alveolar epithelial cells, even though these two molecules are usually expressed in a mutually ex- clusive way. Three-dimensionally cultured HuL cells differentiated to form bronchiole-like and alveolus-like organoids. We also uncovered a few bronchiolar epithelial cells expressing both delta Np63 and TTF-1 in the human lung, suggesting that these cells are the cells of origin for HuL cells. Taken together, delta Np63+ TTF-1+ peripheral airway epithelial cells are possibly the human counterpart of mouse DASCs and may offer potential for future regenerative medicine.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

呼吸器領域には，特発性肺線維症や慢性閉塞性肺疾患など根本的な治療法が存在しない慢性疾患が多く，iPS細胞で注目を集める“細胞治療”が将来的にこれら呼吸器領域の難病にも導入される可能性がある．肺は領域ごとにそれぞれ異なる上皮細胞が存在しているが，そのすべてに分化可能な上皮幹細胞の存在は明らかになっていなかった．本研究においてHuL細胞は末梢肺組織の複数部位の上皮細胞を再生しうる上皮幹細胞であることを明らかにすることができ，将来的に再生治療に使用しうる細胞と期待される．