1. Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids.
- Author
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Liu L, Oura S, Markham Z, Hamilton JN, Skory RM, Li L, Sakurai M, Wang L, Pinzon-Arteaga CA, Plachta N, Hon GC, and Wu J
- Subjects
- Animals, Female, Humans, Pregnancy, Cell Differentiation, Embryo, Mammalian, Embryonic Development, Organogenesis, Primates, Embryo Implantation, Gastrulation, Pluripotent Stem Cells metabolism
- Abstract
In vitro stem cell models that replicate human gastrulation have been generated, but they lack the essential extraembryonic cells needed for embryonic development, morphogenesis, and patterning. Here, we describe a robust and efficient method that prompts human extended pluripotent stem cells to self-organize into embryo-like structures, termed peri-gastruloids, which encompass both embryonic (epiblast) and extraembryonic (hypoblast) tissues. Although peri-gastruloids are not viable due to the exclusion of trophoblasts, they recapitulate critical stages of human peri-gastrulation development, such as forming amniotic and yolk sac cavities, developing bilaminar and trilaminar embryonic discs, specifying primordial germ cells, initiating gastrulation, and undergoing early neurulation and organogenesis. Single-cell RNA-sequencing unveiled transcriptomic similarities between advanced human peri-gastruloids and primary peri-gastrulation cell types found in humans and non-human primates. This peri-gastruloid platform allows for further exploration beyond gastrulation and may potentially aid in the development of human fetal tissues for use in regenerative medicine., Competing Interests: Declaration of interests J.W. and L.L. are named inventors on a patent application (applied through the Board of Regents of The University of Texas System, application number 63/510,612; status of application pending) entitled “SYSTEM AND METHODS FOR GENERATION OF HUMAN FETAL PROGENITORS, TISSUES, AND ORGANS FROM CULTURED STEM CELLS” arising from this work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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