TY - JOUR
T1 - Complete human day 14 post-implantation embryo models from naive ES cells
AU - Oldak, Bernardo
AU - Wildschutz, Emilie
AU - Bondarenko, Vladyslav
AU - Comar, Mehmet Yunus
AU - Zhao, Cheng
AU - Aguilera-Castrejon, Alejandro
AU - Tarazi, Shadi
AU - Viukov, Sergey
AU - Pham, Thi Xuan Ai
AU - Ashouokhi, Shahd
AU - Lokshtanov, Dmitry
AU - Roncato, Francesco
AU - Ariel, Eitan
AU - Rose, Max
AU - Livnat, Nir
AU - Shani, Tom
AU - Joubran, Carine
AU - Cohen, Roni
AU - Addadi, Yoseph
AU - Chemla, Muriel
AU - Kedmi, Merav
AU - Keren-Shaul, Hadas
AU - Pasque, Vincent
AU - Petropoulos, Sophie
AU - Lanner, Fredrik
AU - Novershtern, Noa
AU - Hanna, Jacob H.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/10/19
Y1 - 2023/10/19
N2 - The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking1,2. Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs)3. Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions)4. Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13–14 days after fertilization (Carnegie stage 6a). These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior–posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development.
AB - The ability to study human post-implantation development remains limited owing to ethical and technical challenges associated with intrauterine development after implantation1. Embryo-like models with spatially organized morphogenesis and structure of all defining embryonic and extra-embryonic tissues of the post-implantation human conceptus (that is, the embryonic disc, the bilaminar disc, the yolk sac, the chorionic sac and the surrounding trophoblast layer) remain lacking1,2. Mouse naive embryonic stem cells have recently been shown to give rise to embryonic and extra-embryonic stem cells capable of self-assembling into post-gastrulation structured stem-cell-based embryo models with spatially organized morphogenesis (called SEMs)3. Here we extend those findings to humans using only genetically unmodified human naive embryonic stem cells (cultured in human enhanced naive stem cell medium conditions)4. Such human fully integrated and complete SEMs recapitulate the organization of nearly all known lineages and compartments of post-implantation human embryos, including the epiblast, the hypoblast, the extra-embryonic mesoderm and the trophoblast layer surrounding the latter compartments. These human complete SEMs demonstrated developmental growth dynamics that resemble key hallmarks of post-implantation stage embryogenesis up to 13–14 days after fertilization (Carnegie stage 6a). These include embryonic disc and bilaminar disc formation, epiblast lumenogenesis, polarized amniogenesis, anterior–posterior symmetry breaking, primordial germ-cell specification, polarized yolk sac with visceral and parietal endoderm formation, extra-embryonic mesoderm expansion that defines a chorionic cavity and a connecting stalk, and a trophoblast-surrounding compartment demonstrating syncytium and lacunae formation. This SEM platform will probably enable the experimental investigation of previously inaccessible windows of human early post implantation up to peri-gastrulation development.
UR - http://www.scopus.com/inward/record.url?scp=85173067123&partnerID=8YFLogxK
U2 - 10.1038/s41586-023-06604-5
DO - 10.1038/s41586-023-06604-5
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C2 - 37673118
AN - SCOPUS:85173067123
SN - 0028-0836
VL - 622
SP - 562
EP - 573
JO - Nature
JF - Nature
IS - 7983
ER -