Cell Reports, Journal Year: 2022, Volume and Issue: 39(12), P. 110994 - 110994
Published: June 1, 2022
Language: Английский
Cell stem cell, Journal Year: 2023, Volume and Issue: 30(4), P. 362 - 377.e7
Published: April 1, 2023
Language: Английский
Citations
59
Cell stem cell, Journal Year: 2023, Volume and Issue: 30(9), P. 1148 - 1165.e7
Published: Sept. 1, 2023
Naive human pluripotent stem cells have the remarkable ability to self-organize into blastocyst-like structures ("blastoids") that model lineage segregation in pre-implantation embryo. However, extent which blastoids can recapitulate defining features of post-implantation development remains unexplored. Here, we report cultured on thick three-dimensional (3D) extracellular matrices capture hallmarks early development, including epiblast lumenogenesis, rapid expansion and diversification trophoblast lineages, robust invasion extravillous by day 14. Extended blastoid culture results localized activation primitive streak marker TBXT emergence embryonic germ layers 21. We also show modulation WNT signaling alters balance between fates blastoids. This work demonstrates 3D-cultured offer a continuous integrated vitro system extraembryonic from gastrulation stages.
Language: Английский
Citations
57
Cell, Journal Year: 2023, Volume and Issue: 186(17), P. 3548 - 3557
Published: Aug. 1, 2023
A human embryo's legal definition and its entitlement to protection vary greatly worldwide. Recently, pluripotent stem cells have been used form in vitro models of early embryos that challenged definitions raised questions regarding their usage. In this light, we propose a refined an embryo, suggest "tipping points" for when embryo could eventually be afforded similar embryos, then revisit basic ethical principles might help draft roadmap the gradual, justified usage manner aims maximize benefits society.
Language: Английский
Citations
55
Development, Journal Year: 2023, Volume and Issue: 150(10)
Published: May 15, 2023
Embryo implantation in humans is interstitial, meaning the entire conceptus embeds endometrium before placental trophoblast invades beyond uterine mucosa into underlying inner myometrium. Once implanted, embryo survival pivots on transformation of an anti-inflammatory bed, termed decidua, under homeostatic control natural killer cells. Here, we examine evolutionary context and elaborate remodelling after conception humans. We also discuss interactions between decidualising that regulate interstitial determine fitness. Together, this Review highlights precarious but adaptable nature process.
Language: Английский
Citations
54
Cell stem cell, Journal Year: 2023, Volume and Issue: 30(9), P. 1246 - 1261.e9
Published: Sept. 1, 2023
Recent advances in human blastoids have opened new avenues for modeling early development and implantation. One limitation of our first protocol blastoid generation was relatively low efficiency. We now report an optimized the efficient large quantities high-fidelity from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved derivation and/or maintenance signaling states blastoids. Additionally, we uncovered endometrial stromal effects promoting trophoblast cell survival, proliferation, syncytialization during co-culture with blastocysts. Side-by-side single-cell RNA sequencing revealed similarities differences transcriptome profiles between pre-implantation blastocysts, as well post-implantation cultures, a population resembling migratory trophoblasts Our will facilitate broader use accessible, perturbable, scalable, tractable model
Language: Английский
Citations
51
Cell Research, Journal Year: 2023, Volume and Issue: 33(9), P. 661 - 678
Published: July 17, 2023
Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge lineage development as well underlying mechanisms remains obscure. Using 3D-cultured embryos, herein we report a complete cell atlas the early post-implantation lineages and decipher cellular composition gene signatures epiblast hypoblast derivatives. In addition, develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs extraembryonic cells. E-assembloids, reveal that WNT, BMP Nodal signaling pathways synergistically, but functionally differently, orchestrate Specially, dissect mesoderm endoderm specifications. Finally, improved E-assembloid is developed to recapitulate tissue architectures in pre-gastrulation embryo. Our findings provide development, offers useful model disentangle behaviors interactions drive embryogenesis.
Language: Английский
Citations
49
Cell stem cell, Journal Year: 2023, Volume and Issue: 30(6), P. 867 - 884.e11
Published: May 19, 2023
Gastruloids are 3D structures generated from pluripotent stem cells recapitulating fundamental principles of embryonic pattern formation. Using single-cell genomic analysis, we provide a resource mapping cell states and types during gastruloid development compare them with the in vivo embryo. We developed high-throughput handling imaging pipeline to spatially monitor symmetry breaking report an early spatial variability pluripotency determining binary response Wnt activation. Although gastruloid-core revert pluripotency, peripheral become primitive streak-like. These two populations subsequently break radial initiate axial elongation. By performing compound screen, perturbing thousands gastruloids, derive phenotypic landscape infer networks genetic interactions. Finally, using dual modulation, improve formation anterior existing model. This work provides understand how gastruloids develop generate complex patterns vitro.
Language: Английский
Citations
45
Cell stem cell, Journal Year: 2023, Volume and Issue: 30(12), P. 1569 - 1584
Published: Oct. 18, 2023
Studies of mammalian development have advanced our understanding the genetic, epigenetic, and cellular processes that orchestrate embryogenesis uncovered new insights into unique aspects human embryogenesis. Recent studies now produced first epigenetic maps early embryogenesis, stimulating ideas about reprogramming, cell fate control, potential mechanisms underpinning developmental plasticity in embryos. In this review, we discuss these regulation importance for safeguarding development. We also highlight unanswered questions key challenges remain to be addressed.
Language: Английский
Citations
45
Science Advances, Journal Year: 2024, Volume and Issue: 10(8)
Published: Feb. 23, 2024
The initiation of human pregnancy is marked by the implantation an embryo into uterine environment; however, underlying mechanisms remain largely elusive. To address this knowledge gap, we developed hormone-responsive endometrial organoids (EMO), termed apical-out (AO)–EMO, which emulate in vivo architecture tissue. AO-EMO comprise exposed apical epithelium surface, dense stromal cells, and a self-formed endothelial network. When cocultured with embryonic stem cell–derived blastoids, three-dimensional feto-maternal assembloid system recapitulates critical stages, including apposition, adhesion, invasion. Endometrial epithelial cells were subsequently disrupted syncytial invade fuse cells. We validated fusion syncytiotrophoblasts using blastocysts. Our model provides foundation for investigating interactions, offering valuable insights advancing reproductive medicine.
Language: Английский
Citations
32
Cell stem cell, Journal Year: 2024, Volume and Issue: 31(3), P. 312 - 333
Published: Feb. 20, 2024
Though totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for development of all mammals. Studying these in vivo has been challenging due to limited access ethical constraints, particularly humans. Recent progress led diverse culture adaptations epiblast cells vitro form totipotent pluripotent stem cells, which not only deepen our understanding embryonic but also serve as invaluable resources animal reproduction regenerative medicine. This review delves into hallmarks shedding light on their key molecular functional features.
Language: Английский
Citations
30