Single-Cell Analysis of Embryoids Reveals Lineage Diversification Roadmaps of Early Human Development

Zheng, Yi; Yan, Robin Zhexuan; Kobayashi, Mutsumi; Xiang, Lifeng; Yang, Ran; Goedel, Alexander; Kang, Yu; Xue, Xufeng; Esfahani, Sajedeh Nasr; Liu, Yue; Irizarry, Agnes Resto; Wu, Weisheng; Li, Yunxiu; Ji, Weizhi; Niu, Yuyu; Chien, Kenneth Chang; Li, Tianqing; Shioda, Toshihiro; Fu, Jianping

doi:10.2139/ssrn.3952092

Cited by 1 publication

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“…ISL1 and GABRP are specifically expressed in the amnion but not in the TE lineage of in vitro cultured NHP embryos, at both the transcriptional and protein levels 8 . Furthermore, ISL1 and GABRP are not detectable in the TE of in vitro cultured human blastocysts at both the transcriptional and protein levels 17 .…”

Section: Resultsmentioning

confidence: 91%

A Comprehensive Human Embryogenesis Reference Tool using Single-Cell RNA-Sequencing Data

Zhao

et al. 2021

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Two recent papers in Nature show that human blastocyst-like structures (or blastoids) can be generated from human pluripotent stem cells (Yu et al 2021) or through reprogramming of fibroblasts (Liu et al 2021), respectively. Both papers perform extensive single cell transcriptional analysis and compare blastoid cells with the cells in preimplantation human embryos, leading to a conclusion that the blastoids contain cell lineages corresponding to the epiblast, primitive endoderm and trophectoderm in preimplantation human embryos. Transcriptional analysis is, however, critically dependent on having relevant reference samples, not only of targeted cell types but also of potential alternative cell lineages. For this reason, we have reevaluated the blastoid data with a more comprehensive cellular reference, including extended cultures of blastocysts, several stem cell-based embryo models and a gastrulation stage human specimen. From this reanalysis we resolve that reprogrammed blastoids by Liu et al. fail to generate cells with trophectoderm profiles. Instead, cells identified as trophectoderm lineages in reprogrammed blastoids possess a transcriptional profile more representative of amniotic cells in post-implantation human embryos. Our reanalysis also shows that stem cell-derived blastoids did contain trophectoderm-like cells, highlighting the potential of human blastoids to model blastocyst development.

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Section: Resultsmentioning

confidence: 91%