[New models to study human embryonic development]. / Du nouveau dans les modèles d'étude de l'embryon humain.

Since 2021, assisted reproductive technologies (ART) are available to infertile couples, but also to single women and female couples. The process of in vitro fertilization (IVF) has allowed to cross the threshold of 5 million births worldwide, between 1978 and 2013. However, the failure rate per each IVF cycle is estimated to be around 75%. Therefore, there is a need to better understand human embryonic development in order to improve the success rate of IVF. Study models have evolved significantly in recent years: development of embryo culture, sequencing of the transcriptome of individualized cells, discovery of culture conditions for naive pluripotent stem cells and generation of blastoids. Here, we review these recent advances in human embryo modeling that establish a new knowledge base for improving ART.

Title: Du nouveau dans les modèles d'étude de l'embryon humain. Abstract: Depuis 2021, l'assistance médicale à la procréation (AMP) est accessible aux couples infertiles, mais aussi aux femmes seules et aux couples de femmes. Le processus de fécondation in vitro (FIV) a permis de franchir le seuil de cinq millions de naissances dans le monde, entre 1978 et 2013. Cependant, le taux d'échec à chaque cycle est évalué à environ 75 %. Il est donc nécessaire de mieux comprendre le développement embryonnaire humain afin d'améliorer le taux de succès des FIV. Les modèles d'étude ont beaucoup évolué ces dernières années : mise au point de la culture embryonnaire, séquençage du transcriptome de cellules individualisées, découverte des conditions de culture de cellules souches pluripotentes naïves et génération de blastoïdes. Nous revenons dans cette revue sur ces avancées récentes concernant la modélisation de l'embryon humain, qui établissent un nouveau socle de connaissances pour améliorer l'AMP.

Integrated pseudotime analysis of human pre-implantation embryo single-cell transcriptomes reveals the dynamics of lineage specification.

Understanding lineage specification during human pre-implantation development is a gateway to improving assisted reproductive technologies and stem cell research. Here we employ pseudotime analysis of single-cell RNA sequencing (scRNA-seq) data to reconstruct early mouse and human embryo development. Using time-lapse imaging of annotated embryos, we provide an integrated, ordered, and continuous analysis of transcriptomics changes throughout human development. We reveal that human trophectoderm/inner cell mass transcriptomes diverge at the transition from the B2 to the B3 blastocyst stage, just before blastocyst expansion. We explore the dynamics of the fate markers IFI16 and GATA4 and show that they gradually become mutually exclusive upon establishment of epiblast and primitive endoderm fates, respectively. We also provide evidence that NR2F2 marks trophectoderm maturation, initiating from the polar side, and subsequently spreads to all cells after implantation. Our study pinpoints the precise timing of lineage specification events in the human embryo and identifies transcriptomics hallmarks and cell fate markers.

Induction of Human Trophoblast Stem Cells from Somatic Cells and Pluripotent Stem Cells.

Human trophoblast stem cells (hTSCs) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the placenta. However, access to human embryos and first-trimester placentas is limited, thus preventing the establishment of hTSCs from diverse genetic backgrounds associated with placental disorders. Here, we show that hTSCs can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (1) somatic cell reprogramming of adult fibroblasts with OCT4, SOX2, KLF4, MYC (OSKM) and (2) cell fate conversion of naive and extended pluripotent stem cells. The resulting induced/converted hTSCs recapitulated hallmarks of hTSCs including long-term self-renewal, expression of specific transcription factors, transcriptomic signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSCs and show that these cells resemble day 8 cytotrophoblasts. Altogether, hTSC lines of diverse genetic origins open the possibility to model both placental development and diseases in a dish.