TY - JOUR
KW - Blastocyst
KW - Cell Survival
KW - Embryo Implantation
KW - Humans
KW - Signal Transduction
KW - Trophoblasts
KW - endometrial stromal cells
KW - human blastocyst-like structures
KW - human blastocysts
KW - human blastoids
KW - human integrated stem cell embryo model
KW - human peri-implantation development
KW - naive human embryonic stem cells
KW - naive human induced pluripotent stem cells
KW - syncytiotrophoblast
AU - Leqian Yu
AU - Deirdre Logsdon
AU - Carlos A. Pinzon-Arteaga
AU - Jialei Duan
AU - Toshihiko Ezashi
AU - Yulei Wei
AU - Ana Elisa Ribeiro Orsi
AU - Seiya Oura
AU - Lizhong Liu
AU - Lei Wang
AU - Kun Liu
AU - Xiaoyun Ding
AU - Linfeng Zhan
AU - Junfei Zhang
AU - Asrafun Nahar
AU - Caitlen Stobbe
AU - Mandy Katz-Jaffe
AU - William B. Schoolcraft
AU - Tao Tan
AU - Gary C. Hon
AU - Ye Yuan
AU - Jun Wu
AB - 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.
BT - Cell Stem Cell
DA - 2023-09-07
DO - 10.1016/j.stem.2023.08.002
IS - 9
LA - eng
N2 - 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.
PY - 2023
SP - 1246
EP - 1261.e9
T2 - Cell Stem Cell
TI - Large-scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal cross talk
VL - 30
SN - 1875-9777
ER -