The direct differentiation method of renal tubular cells by master transcription factors identified from TF-inducible human ES bank

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670432
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Hiroshi Itoh 慶應義塾大学, 医学部, 教授 (40252457)
• Co-Investigator(Renkei-kenkyūsha): Koh Minoru 慶應義塾大学, 医学部(信濃町), 教授 (50631199) ; Monkawa Toshiaki 慶應義塾大学, 医学部(信濃町), 教授 (80286484)
• Research Collaborator: Hiratsuka Ken 慶應義塾大学, 医学部(信濃町), 博士課程大学院生
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ES細胞 / 尿細管 / 転写因子

Outline of Final Research Achievements

To find transcription factors which promote differentiation towards renal tubular cells, we utilize the human ES lines with doxycycline-controllable transcription factors (TF-inducible hES bank) and performed exhaustive search for DNA microarray data. Some candidate transcription factors were identified by in silico analysis. By using the lipofection method, we transfected the synthetic mRNA of target transcription factors to human ES cells, and cultured them. Five days after the transfection, we were able to observe characteristic morphological changes in the differentiated cells. The mRNA expression of OSR1, AQP1, and MEGALIN were increased. Moreover, the protein expression of AQP1 and LTL were also detected in the differentiated cells. We identified specific transcription factors for differentiation toward proximal tubular cells, and demonstrated that the differentiation of proximal tubular cell phenotype from human ES cells by a novel method using synthetic mRNA.

Free Research Field

腎臓内分泌代謝