最先端研究セミナー

 

講演者：　大串　雅俊（京都大学ウイルス・再生医科学研究所　発生システム制御分野 准教授）

演題：　Do human embryonic stem cells have trophoblast competence?

 

日時： 2021年4月28日（水）12:00- 13:00

 

Abstract:

Embryogenesis is a substantially diverse process across species in embryonic morphology,tissue allocations, molecular signatures, and fate specification mechanisms. In the field of mammalian developmental biology, mice have taken center stage as a primary modelanimal. Mouse studies have established the concept that the segregation of inner cell mass (ICM), which gives rise to all tissues of the fetus, and trophectoderm, which differentiates into the major portion of the placenta, occurs precisely at a genetically programmed timing, and the following developmental paths of each lineage are never crossed. In line with this, mouse embryonic stem cells (ESCs), which are derived from ICM cells of
blastocysts, retain pluripotency and therefore can differentiate into cells of all three germ layers, but lost the competence to differentiate into trophoblast lineages (Rossant J.2018).
The consensus that ESCs never differentiate to trophoblast had been challenged by a surprising report showing that “human” ESCs were converted into differentiated cells with unique properties for placental cells just by exposing them to BMP4 (Xu et al, 2002). The reliability of the ESC-to-trophoblast differentiation has been under intense argument for the past decades (Roberts et al, 2014), maybe because it contains a striking contradiction to the developmental dogma that validated in mouse studies. Besides, whether trophoblast differentiation from human ESCs recapitulates any biological phenomenon has remained an open question.
Recently, we found that human ESCs can differentiate into trophoblast-like cells without exogenous inducer such as BMP ligands, suggesting that despite their cellular property reminiscent of post-implantation epiblast, primate ESCs retain trophoblast competence. We are now trying to characterizing the cellular properties of ESC-derived trophoblastlike cells (TBLCs) and deciphered the molecular mechanisms for the cell state transition linking pluripotency dissolution to TBLC fate specification.

 

References：
Rossant J, Annu. Rev. Genet. 52, 185-201, 2018
Xu RH et al., Nat. Biotechnol. 12, 1261-1264, 2002
Roberts RM, et al, Reproduction 147, D1-12, 2014

 

 

担当分野：多能性幹細胞　丹羽（内線：6606）

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