PT  - JOURNAL ARTICLE
AU  - Cheng Zhao
AU  - Alvaro Plaza Reyes
AU  - John Paul Schell
AU  - Jere Weltner
AU  - Nicolás Ortega
AU  - Yi Zheng
AU  - Åsa K. Björklund
AU  - Janet Rossant
AU  - Jianping Fu
AU  - Sophie Petropoulos
AU  - Fredrik Lanner
TI  - Reprogrammed iBlastoids contain amnion-like cells but not trophectoderm
AID  - 10.1101/2021.05.07.442980
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.07.442980
4099  - http://biorxiv.org/content/early/2021/05/07/2021.05.07.442980.short
4100  - http://biorxiv.org/content/early/2021/05/07/2021.05.07.442980.full
AB  - Two recent papers in Nature show that human blastocyst-like structures (or blastoids) can be generated from human pluripotent stem cells1 or through reprogramming of fibroblasts2, respectively. Both papers perform extensive single cell transcriptional analysis and compare blastoid cells with the cells in preimplantation human embryos3,4, 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 blastoids1 did contain trophectoderm-like cells, highlighting the potential of human blastoids to model blastocyst development.Competing Interest StatementThe authors have declared no competing interest.