A comparative analysis of blastoid models through single-cell transcriptomics

Ali Balubaid; Samhan Alsolami; Narsis A Kiani; David Gomez-Cabrero; Mo Li; Jesper Tegner

doi:10.1016/j.isci.2024.111122

A comparative analysis of blastoid models through single-cell transcriptomics

iScience. 2024 Oct 11;27(11):111122. doi: 10.1016/j.isci.2024.111122. eCollection 2024 Nov 15.

Authors

Ali Balubaid¹, Samhan Alsolami¹, Narsis A Kiani^{2

3}, David Gomez-Cabrero^{1

4}, Mo Li¹, Jesper Tegner^{1

3

5

6}

Affiliations

¹ Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
² Algorithmic Dynamic Lab, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
³ Unit of Computational Medicine, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, L8:05, SE-171 76 Stockholm, Sweden.
⁴ Translational Bioinformatics Unit, Navarrabiomed, Complejo Hospitalario de Navarra (CHN), Universidad Pu'blica de Navarra (UPNA), IdiSNA, Pamplona, Spain.
⁵ Computer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
⁶ Science for Life Laboratory, Tomtebodavagen 23A, SE-17165 Solna, Sweden.

Abstract

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.

Keywords: Developmental biology; Stem cells research; Transcriptomics.