Investigation of the molecular basis of extraembryonic lineage specification in humans

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Tohoku University
• Principal Investigator: Hiroaki Okae 東北大学, 医学系研究科, 准教授 (10582695)
• Co-Investigator(Kenkyū-buntansha): 有馬 隆博 東北大学, 医学系研究科, 教授 (80253532)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ヒト胎盤 / 胎盤トロフォブラスト幹（TS)細胞 / エピジェネティクス / ダイレクトリプログラミング

Outline of Final Research Achievements

A mammalian zygote undergoes cleavage divisions to form a blastocyst that is composed of inner cell mass (ICM) and trophectoderm (TE). In mice, many transcription factors including CDX2 and EOMES have been identified as essential for the specification of the TE lineage. However, little is known about how the TE lineage is specified in human preimplantation embryos. This study aimed to identify factors involved in this process. To this end, we identified transcription factors specifically expressed in undifferentiated human TS cells. Although it turned out to be difficult to derive induced TS (iTS) cells from somatic cells with these transcription factors, we successfully converted human ES/iPS cells into iTS cells by overexpressing GATA2, GATA3, or TFAP2A. These transcription factors may be involved in the regulation of early lineage specification in humans.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

ヒトiTS細胞の誘導に有効であったGATA2、GATA3、TFAP2Aは、マウスの胎盤発生においても重要な役割を担うことが報告されている。一方、CDX2やEOMESを用いてヒトiTS細胞を誘導することはできない。よって、TE系譜への運命決定機構は、ヒトとマウスの間で一部保存されていることが明らかとなった。ヒト着床前胚における細胞運命決定機構の理解は、不妊や流産の原因の解明や、安全な生殖補助医療の提供などに役立つと期待される。