Reprogramming epiblast stem cells into pre-implantation blastocyst cell-like cells

Abstract

Summary Recently, a new wave of synthetic embryo systems (SESs) has been established from cultured cells for efficient and ethical embryonic development research. We recently reported our epiblast stem cell (EPISC) reprogramming SES that generates numerous blastocyst (BC)-like hemispheres (BCLH) with pluripotent and extraembryonic cell features detected by microscopy. Here, we further explored the system over key time points with single-cell RNA-sequencing analysis. We found broad induction of the 2C-like reporter MERVL and RNA velocities diverging to three major cell populations with gene expression profiles resembling those of pluripotent epiblast, primitive endoderm, and trophectoderm. Enrichment of those three induced BC-like cell fates involved key gene-regulatory networks, zygotic genome activation-related genes, and specific RNA splicing, and many cells closely resembled in silico models. This analysis confirms the induction of extraembryonic cell populations during EPISC reprogramming. We anticipate that our unique BCLH SES and rich dataset may uncover new facets of cell potency, improve developmental biology, and advance biomedicine.

Derivation of functional trophoblast stem cells from primed human pluripotent stem cells

“…However, unlike naive mouse ESCs, naive human ESCs have recently been shown by multiple groups to readily give rise to trophoblast ( Cinkornpumin et al., 2020 ; Dong et al., 2020 ; Guo et al., 2021 ; Io et al., 2021 ), suggesting greater plasticity of human ESCs. In addition, it has been shown that media containing BMP4 induces chromatin remodeling in primed mouse ESCs ( Kime et al., 2016 ; Yu et al., 2020 ), inducing some cells toward a naive, and even 2C-like, fate, while producing TE-like features in other cells ( Kime et al., 2019 ; Tomoda et al., 2021 ). Our own analysis of primed hPSCs treated with a BMP4-containing medium points to a direct conversion of these cells to a TE-like fate, following 4 days of treatment with BMP4 and IWP2, with induction of only one naive pluripotency marker noted.…”

Ethical, legal, regulatory, and policy issues concerning embryoids: a systematic review of the literature

“…Nature. 2020;577(7791):459–60 [ 32 ] Tomoda K, Hu H, Sahara Y, Sanyal H, Takasato M, Kime C. Reprogramming epiblast stem cells into pre-implantation blastocyst cell-like cells. Stem Cell Rep. 2021;16(5):1197–209 [ 42 ] Tomoda K, Kime C. Synthetic embryology: Early mammalian embryo modeling systems from cell cultures.…”

Computational approach to evaluate scRNA-seq data quality and gene body coverage with SkewC

“…In our previous publications 3 , 4 we demonstrated the implementation, integration, and utilization of SkewC in scRNA-seq data analysis.…”