A comparative analysis of blastoid models through single-cell transcriptomics
Ali Balubaid,
Samhan Alsolami,
Narsis A. Kiani,
David Gomez-Cabrero,
Mo Li,
Jesper Tegner
Affiliations
Ali Balubaid
Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; Corresponding author
Samhan Alsolami
Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia
Narsis A. Kiani
Algorithmic Dynamic Lab, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden; Unit of Computational Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, L8:05, SE-171 76 Stockholm, Sweden
David Gomez-Cabrero
Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; Translational Bioinformatics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pu'blica de Navarra (UPNA), IdiSNA, Pamplona, Spain
Mo Li
Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; Corresponding author
Jesper Tegner
Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; Unit of Computational Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, L8:05, SE-171 76 Stockholm, Sweden; Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; Science for Life Laboratory, Tomtebodavagen 23A, SE-17165 Solna, Sweden; Corresponding author
Summary: Pluripotent-stem-cell-derived blastocyst-like structures (blastoids) offer insights into early human embryogenesis (5–10 days post-fertilization). The similarity between blastoids and human blastocysts remains uncertain. To investigate, we evaluated single-cell RNA sequencing (scRNAseq) data from seven blastoid models, comparing them to peri-implantation blastocysts. We quantified cell-type composition, transcriptomic overlap, lineage profiles, and developmental propensities for primary (epiblast, primitive endoderm, trophectoderm) and potential lineages (amnion, extravillous cytotrophoblasts, syncytial trophoblasts). Blastoids from extended pluripotent stem cells (EPSCs) are distinct from those from naive pluripotent stem cells (nPSCs), which cluster closer to natural blastocysts. EPSC-blastoids show a higher composition of primitive endoderm cells and ambiguous cells with notable endoderm signatures. Starting cell lines' scRNAseq analysis reveals higher heterogeneity in nPSCs and prevalent amnionic signatures in EPSCs. These findings suggest gene expression heterogeneity in founding cells influences blastoid lineage differentiation, aiding protocol optimization for better human embryogenesis models.
