Dynamics of trophoblast differentiation in peri-implantation–stage human embryos

Abstract

Single-cell RNA sequencing of cells from cultured human blastocysts has enabled us to define the transcriptomic landscape of placental trophoblast (TB) that surrounds the epiblast and associated embryonic tissues during the enigmatic day 8 (D8) to D12 peri-implantation period before the villous placenta forms. We analyzed the transcriptomes of 3 early placental cell types, cytoTB (CTB), syncytioTB (STB), and migratoryTB (MTB), picked manually from cultured embryos dissociated with trypsin and were able to follow sublineages that emerged from proliferating CTB at the periphery of the conceptus. A unique form of CTB with some features of STB was detectable at D8, while mature STB was at its zenith at D10. A form of MTB with a mixed MTB/CTB phenotype arose around D10. By D12, STB generation was in decline, CTB had entered a new phase of proliferation, and mature MTB cells had begun to move from the main body of the conceptus. Notably, the MTB transcriptome at D12 indicated enrichment of transcripts associated with IFN signaling, migration, and invasion and up-regulation of HLA-C, HLA-E, and HLA-G. The STB, which is distinct from the STB of later villous STB, had a phenotype consistent with intense protein export and placental hormone production, as well as migration and invasion. The studies show that TB associated with human embryos is in rapid developmental flux during peri-implantation period when it must invade, signal robustly to the mother to ensure that the pregnancy continues, and make first contact with the maternal immune system.

Mechanisms of human embryo development: from cell fate to tissue shape and back

“…Co-cultures with endometrial cells have traditionally been used to explore the crosstalk between the embryo and the uterus ( Weimar et al, 2013 ; Lindenberg et al, 1985 ), but whether the embryo undergoes proper morphogenesis in this setting is unclear. Recently, human embryos have been cultured up to day 13 in vitro , thus permitting insight into the major morphological transformations of post-implantation human development – TE differentiation ( West et al, 2019 ), amniotic cavitation (see Glossary, Box 1 ) and primary yolk sac (see Glossary, Box 1 ) formation – in the absence of interactions with maternal tissues ( Deglincerti et al, 2016 ; Shahbazi et al, 2016 ). This culture method has been taken forward by the addition of a 3D matrix, which allows amnion (see Glossary, Box 1 ) specification and further development up to the gastrula stage ( Xiang et al, 2019 ).…”

Potential SARS-CoV-2 interactions with proteins involved in trophoblast functions – An in-silico study

“…Genes/proteins involved in critical placental functions or that are differentially expressed in placental pathology were also obtained by text mining, and literature search of studies involving such analysis – the genes that are upregulated in cytotrophoblasts, syncytiotrophoblasts and migratory trophoblasts were obtained from a study by West et al [ 28 ], and the differentially expressed genes in gestational diabetes mellitus from a study by Radaelli et al [ 29 ].…”

An In Silico Analysis of Potential SARS-CoV-2 Interactions with Proteins Involved in Placental Functions

“…Genes/proteins involved in critical placental functions or that are differentially expressed in placental pathology were also obtained by text mining, and literature search of studies involving such analysis -the genes that are upregulated in cytotrophoblasts, syncytiotrophoblasts and migratory trophoblasts were obtained from a study by West et al, (23) and the differentially expressed genes in gestational diabetes mellitus from a study by Radaelli et al(24)…”