@article{2561, keywords = {Blastocyst, Cell Survival, Embryo Implantation, Humans, Signal Transduction, Trophoblasts, endometrial stromal cells, human blastocyst-like structures, human blastocysts, human blastoids, human integrated stem cell embryo model, human peri-implantation development, naive human embryonic stem cells, naive human induced pluripotent stem cells, syncytiotrophoblast}, author = {Leqian Yu and Deirdre Logsdon and Carlos A. Pinzon-Arteaga and Jialei Duan and Toshihiko Ezashi and Yulei Wei and Ana Elisa Ribeiro Orsi and Seiya Oura and Lizhong Liu and Lei Wang and Kun Liu and Xiaoyun Ding and Linfeng Zhan and Junfei Zhang and Asrafun Nahar and Caitlen Stobbe and Mandy Katz-Jaffe and William B. Schoolcraft and Tao Tan and Gary C. Hon and Ye Yuan and Jun Wu}, title = {Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk}, abstract = {Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. One limitation of our first protocol for human blastoid generation was relatively low efficiency. We now report an optimized protocol for the efficient generation of large quantities of high-fidelity human blastoids from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved in the derivation and/or maintenance of the signaling states in human blastoids. Additionally, we uncovered endometrial stromal effects in promoting trophoblast cell survival, proliferation, and syncytialization during co-culture with blastoids and blastocysts. Side-by-side single-cell RNA sequencing revealed similarities and differences in transcriptome profiles between pre-implantation blastoids and blastocysts, as well as post-implantation cultures, and uncovered a population resembling early migratory trophoblasts during co-culture with endometrial stromal cells. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, and tractable model for human blastocysts.}, year = {2023}, journal = {Cell Stem Cell}, volume = {30}, pages = {1246-1261.e9}, month = {2023-09-07}, issn = {1875-9777}, doi = {10.1016/j.stem.2023.08.002}, language = {eng}, }