Primary specification of blastocyst trophectoderm by scRNA-seq: New insights into embryo implantation

Liu, Dandan; Chen, Yidong; Ren, Yixuan; Yuan, Peng; Wang, Nan; Liu, Qiang; Yang, Cen; Yan, Zhiqiang; Yang, Ming; Wang, Jing; Lian, Ying; Yan, Jie; Zhai, Fan; Nie, Yanli; Zhu, Xiaohui; Chen, Yuan; Li, Rong; Chang, Hsun‐Ming; Qiao, Jie

doi:10.1126/sciadv.abj3725

Cited by 29 publications

(28 citation statements)

References 76 publications

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“…Genes implicated in the literature to correspond with 13 of our cell type annotations are represented in the 3012 cESFW gene set (Cockburn and Rossant 2010; Taubenschmid-Stowers et al 2022; Giuliano G. Stirparo et al 2018; M. Singh et al 2023; Corujo-Simon, A. H. Radley, and Nichols 2023; Liu et al 2022; Zadora et al 2017; Yue et al 2020; Yabe et al 2016; Yang et al 2021). Such genes show specific gene expression in the UMAP embedding (Fig 3E, Fig 5A Fig S3).…”

Section: Resultsmentioning

confidence: 99%

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Branching topology of the human embryo transcriptome revealed by entropy sort feature weighting

Radley,

Smith

2023

Preprint

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Single cell transcriptomics (scRNA-seq) transforms our capacity to define cell states and reveal developmental trajectories. Resolution is challenged, however, by high dimensionality and noisy data. Analysis is therefore typically performed after sub-setting to highly variable genes (HVGs). However, existing HVG selection techniques have been found to have poor agreement with one another, and tend to be biased towards highly expressed genes. Entropy sorting provides an alternative mathematical framework for feature subset selection. Here we implement continuous entropy sort feature weighting (cESFW). On synthetic datasets, cESFW outperforms HVG selection in distinguishing cell state specific genes. We apply cESFW to six merged scRNA-seq datasets spanning human early embryo development. Without smoothing or augmenting the raw counts matrices, cESFW generates a high-resolution embedding displaying coherent developmental progression from 8-cell to post-implantation stages, delineating 15 distinct cell states. The embedding highlights sequential lineage decisions during blastocyst development while unsupervised clustering identifies branch point populations. Cells previously claimed to lack a developmental trajectory reside in the first branching region where morula differentiates into Inner Cell Mass (ICM) or Trophectoderm (TE). We quantify the relatedness of pluripotent stem cell cultures to embryo cell types and identify naïve and primed marker genes conserved across culture conditions and the human embryo. Finally, by identifying genes with specifically enriched and dynamic expression during blastocyst formation, we provide markers for staging lineage progression from morula to blastocyst. Together these analyses indicates that cESFW provides the ability to reveal gene expression dynamics in scRNA-seq data that HVG selection may can to elucidate.

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Section: Resultsmentioning

confidence: 99%

“…Such genes show specific gene expression in the UMAP embedding (Fig 3E, Fig 5A Fig S3). Mural trophectoderm (TE) lacks validated specific markers but is known to express HAND1 (Liu et al 2022). Although HAND1 is not captured in the cESFW gene set, it shows relatively specific day 6/7 Mural TE expression on our UMAP embedding Fig S3).…”

Section: Resultsmentioning

confidence: 99%

Branching topology of the human embryo transcriptome revealed by entropy sort feature weighting

Radley,

Smith

2023

Preprint

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“…Meanwhile, with the rapid development of singlecell RNA sequencing and single-cell multiomics sequencing, peri-implantation embryos have been systematically analyzed, providing deeper insight into the complex molecular mechanisms underlying embryo implantation. 13,14 In mice Endometrial receptivity is under the precise control of ovarian steroid hormones, as well as a variety of transcription factors, growth factors, cytokines, and lipid signaling mediators. It is widely accepted that estrogen and progesterone play predominant roles in uterine receptivity.…”

Section: Reviewmentioning

confidence: 99%

“…Ex utero cultured monkey embryos largely recapitulated key events of in vivo development, providing a robust and reproducible platform for studying primate embryogenesis ex utero. Meanwhile, with the rapid development of single-cell RNA sequencing and single-cell multiomics sequencing, peri-implantation embryos have been systematically analyzed, providing deeper insight into the complex molecular mechanisms underlying embryo implantation 13,14 …”

Section: Recent Progress In Embryo Implantation Research In Humans An...mentioning

confidence: 99%

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

Bao,

Wang

2024

Maternal Fetal Med

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This review aimed to summarize the major progress in maternal-fetal medicine achieved by Chinese scientists in recent years. PubMed was systematically searched from January 2020 to November 2023. Publications that reported the progress in embryo implantation, placentation, and parturition made by Chinese scientists in the last 3 years were selected. The milestone events during gestation, embryo implantation, endometrial decidualization, placentation, and parturition are pivotal to a successful pregnancy. Embryo implantation requires intricate interactions between implantation-competent blastocysts and receptive endometrium. To adapt to pregnancy, endometrial stromal cells transform into specialized decidual cells, which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in mice. With embryonic development, the placenta forms to support fetal growth until parturition. The maternal-fetal interface is composed of diverse cell types, including endometrial decidual cells, placental trophoblast cells, endothelial cells, and various immune cells, a sophisticated interplay among which contributes to the maintenance of pregnancy. Near term, the uterus transitions from quiescence to contractility, in preparation for delivery. Disruptions to these events lead to pregnancy-related disorders such as repeated implantation failure, recurrent pregnancy loss, preeclampsia, fetal growth restriction, preterm birth, and infertility. In recent years, Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy events. Chinese scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine research in recent years, highlighting future research directions in this field.

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“…Moreover, FGF, STAT, SMAD, and Hippo signaling pathways are enhanced in the mice polar TE [32]. Different from polar TE enjoying the potential to interact with the endometrium and to form an implantation site in humans, mice attach to and invade the endometrium via the mural TE [33]. Consistently, OVOL1 , GATA2 , GATA3 , TFAP2C , and CGA upregulate in both mice mural TE and human polar TE to fulfill the function of adhesive and invading phenotype (Table 1) [33].…”

Section: Introductionmentioning

confidence: 99%

Early differentiation and gene expression characteristics of trophoblast lineages

Qin

et al. 2023

Biology of Reproduction

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With the development of the embryo, the totipotent blastomere undergoes the first lineage decision to the inner cell mass (ICM) and the trophectoderm (TE). The ICM forms the fetus while the TE forms the placenta, which is one of the most unique organs in mammals serving as the interface between maternal and fetal. Proper trophoblast lineage differentiation is crucial for correct placental and fetal development, including the TE progenitor self-renewal and its differentiation toward mononuclear cytotrophoblast (CTB), which later either develops into invasive extravillous trophoblast (EVT), remodeling the uterine vascular, or fuses into multinuclear syncytiotrophoblast (STB), secreting pregnancy-sustaining hormone. Aberrant differentiation and gene expression of trophoblast lineage is associated with severe pregnancy disorders and fetal growth restriction. This review focuses on the early differentiation and key regulatory factors of trophoblast lineage, which have been poorly elucidated. Meanwhile, the recent development of trophoblast stem cells (TSC), trophectoderm stem cells (TESC), and blastoids derived from pluripotent stem cells bring the accessible model to investigate the profound mystery of embryo implantation and placentation were also summarized.

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Primary specification of blastocyst trophectoderm by scRNA-seq: New insights into embryo implantation

Cited by 29 publications

References 76 publications

Branching topology of the human embryo transcriptome revealed by entropy sort feature weighting

Branching topology of the human embryo transcriptome revealed by entropy sort feature weighting

Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition

Early differentiation and gene expression characteristics of trophoblast lineages

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