@article{49ac60a5978a4da1aaa44773f470f389,
title = "3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages",
abstract = "Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures (“blastoids”) that model lineage segregation in the pre-implantation embryo. However, the extent to which blastoids can recapitulate the defining features of human post-implantation development remains unexplored. Here, we report that blastoids cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks of early post-implantation development, including epiblast lumenogenesis, rapid expansion and diversification of trophoblast lineages, and robust invasion of extravillous trophoblast cells by day 14. Extended blastoid culture results in the localized activation of primitive streak marker TBXT and the emergence of embryonic germ layers by day 21. We also show that the modulation of WNT signaling alters the balance between epiblast and trophoblast fates in post-implantation blastoids. This work demonstrates that 3D-cultured blastoids offer a continuous and integrated in vitro model system of human embryonic and extraembryonic development from pre-implantation to early gastrulation stages.",
keywords = "blastocyst, blastoid, epiblast, gastrulation, naive pluripotency, post-implantation development, primitive endoderm, primitive streak, stem cells, trophectoderm",
author = "Karvas, {Rowan M.} and Zemke, {Joseph E.} and Ali, {Syed Shahzaib} and Eric Upton and Eshan Sane and Fischer, {Laura A.} and Chen Dong and Park, {Kyoung mi} and Fei Wang and Kibeom Park and Senyue Hao and Brian Chew and Brittany Meyer and Chao Zhou and Sabine Dietmann and Theunissen, {Thorold W.}",
note = "Funding Information: We thank the Genome Technology Access Center at Washington University for assistance with scRNA-seq and Peter Bayguinov with the Washington University Center for Cellular Imaging and Biology Imaging Facility for assistance with imaging. We thank Drs. Lilianna Solnica-Krezel, Kristen Kroll, and Shafqat Khan for critical reading of the manuscript. This work was supported by grants from the Children{\textquoteright}s Discovery Institute , the Shipley Foundation Program for Innovation in Stem Cell Science , and the Edward Mallinckrodt, Jr. Foundation to T.W.T. Federal NIH funds were not used to develop integrated 3D models of human embryonic development. Funding Information: We thank the Genome Technology Access Center at Washington University for assistance with scRNA-seq and Peter Bayguinov with the Washington University Center for Cellular Imaging and Biology Imaging Facility for assistance with imaging. We thank Drs. Lilianna Solnica-Krezel, Kristen Kroll, and Shafqat Khan for critical reading of the manuscript. This work was supported by grants from the Children's Discovery Institute, the Shipley Foundation Program for Innovation in Stem Cell Science, and the Edward Mallinckrodt, Jr. Foundation to T.W.T. Federal NIH funds were not used to develop integrated 3D models of human embryonic development. R.M.K. J.E.Z, C.D. and L.A.F. optimized the conditions for blastoid generation from naive hPSCs under the supervision of T.W.T. R.M.K. developed the methodology for extended blastoid culture under the supervision of T.W.T. E.S. K.P. B.C. and B.M. assisted R.M.K. with experiments. E.U. and S.S.A. analyzed scRNA-seq data under the supervision of S.D. F.W. K.P. and S.H. performed OCT imaging under the supervision of C.Z. R.M.K. and T.W.T. analyzed and interpreted the results and wrote the paper with input from the other authors. R.M.K. and T.W.T. are co-inventors on a patent application related to the extended culture of human blastoids on 3D matrices. One or more of the authors of this paper self-identifies as a member of the LGBTQIA+ community. Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
month = sep,
day = "7",
doi = "10.1016/j.stem.2023.08.005",
language = "English",
volume = "30",
pages = "1148--1165.e7",
journal = "Cell Stem Cell",
issn = "1934-5909",
number = "9",
}