This is my third paper at UTSW (co-authored). The paper investigates improving the efficiency of creating human blastoids and co-culturing them with endometrial stromal cells. I was mainly responsible for additional experiments on the co-culture of endometrial stromal cells and blastoids, including sample preparation for IF and scRNA-seq. I remember struggling with these experiments initially due to their lack of reproducibility. Although there is still room for improvement in stem cell-derived embryo model technologies, including blastoids, I believe we are making steady progress one step at a time.
UTSWでの三本目の論文です(共著)。ヒトBlastoidの作成効率向上とEndometrial Stromal Cellとの共培養を検討した論文で、私は、主に、Endometrial Stromal CellとBlastoidの共培養の追加実験(IFとscRNA-seqのサンプル調整)を担当しました。UTSWに来てから一番最初にやっていた実験で、まったく再現性がとれず苦労したのを思い出します。Blastoidを含めた幹細胞由来胚モデルの技術にはまだまだ改善の余地は残りますが、一歩ずつ着実に進んでいるように思います。
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.