Renal tubular cells derived from human ES cells and hepatocytes by transcription factor administration

2017 Fiscal Year Final Research Report

• Project/Area Number: 16H07177
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Hiratsuka Ken 慶應義塾大学, 医学部(信濃町), 助教 (80594481)
• Research Collaborator: KO Minoru 慶應義塾大学, 医学部, 教授 (50631199)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Keywords: ヒトES細胞 / 転写調節因子 / リプログラミング / 腎臓再生

Outline of Final Research Achievements

We utilized the transcription factor (TF)-inducible human ES lines, analyzed correlation of gene expression response to the induction of human TFs with tissue-specific gene expression in silico, and identified candidate TFs for differentiating towards renal lineages. Based on in-silico analysis, we have identified a set of four TFs that induce nephron progenitor cells (NPCs) and another set of four TFs that help differentiate toward pretubular aggregate-like cells. Two days after the transfection of the first set of four TFs together into hESCs, NPCs were induced efficiently (~92%). Subsequent administration of the second set of four TFs transfection induced differentiation into pretubular aggregate-like cells. On day 14, epithelial characteristic changes and multi-segmented kidney structures containing podocyte, proximal tubules, and distal tubules were observed in 3D cultures. RNA-Seq analysis also showed the global expression profile closely resembled human kidney profile.

Free Research Field

腎臓再生