Direct reprogramming of human fibroblasts into hematopoietic cells mainly using ETV2

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670470
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Keio University
• Principal Investigator: Morita Rimpei 慶應義塾大学, 医学部, 准教授 (00362541)
• Co-Investigator(Renkei-kenkyūsha): YOSHIMURA Akihiko 慶應義塾大学, 医学部, 教授 (90182815)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 造血幹細胞 / 転写因子 / エピジェネティクス

Outline of Final Research Achievements

An ETS family transcription factor ETV2 is essential for hemato-endothelial development in embryo. We have reported that human adult skin fibroblasts directly convert into functional endothelial cells by transducing ETV2.
Interestingly we found that ETV2-transduced human adult skin fibroblasts also expressed RUNX1, TAL1, and GATA2, which were transcription factors essential for hematopoiesis. Thus to generate hematopoietic cells from fibroblasts, we transduced not only ETV2 but also 20 kinds of transcription factors essential for hematopoiesis into human adult skin fibroblasts, then co-cultured them with OP9 stroma cells in the presence of SCF, FLT3L, TPO, IL-3, and IL-6 for four weeks. Consequently we detected CD45+c-Kit+ hematopoietic-like cells by FACS analysis. Our results may leads to generation of functional hematopoietic cells from individual skin in the future.

Free Research Field

免疫学