In a new study, researchers from Kunming University of Science and Technology, China; China Agricultural University, China; the Chinese Academy of Sciences; and the University of Texas Southwestern Medical Center have developed a novel culture system that co-cultivates embryonic stem cells (ESCs) and extraembryonic stem cells (ESCs), which may provide insights into the causes of congenital malformations and early developmental disorders. which has the potential to provide important insights into the causes of congenital malformations and early developmental disorders. The results of the study were published online Dec. 4, 2023, in the journal Cell under the title "Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture The paper is titled "Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture. The corresponding authors of the paper are Dr. Weizhi Ji and Dr. Tao Tan from Kunming University of Science and Technology and Dr. Jun Wu from The University of Texas Southwestern Medical Center.
Dr. Wu said, "These findings demonstrate significant advances in stem cell and developmental biology through the development of a unified stem cell culture system. The use of this novel system not only deepens our understanding of the interactions between embryonic and extraembryonic cells during embryogenesis, but also lays the foundation for the construction of more accurate models of embryonic development and improved stem cell differentiation protocols."
In addition to outlining new unified growth conditions for embryonic and extraembryonic stem cells, this new study reveals key interactions between different embryonic and extraembryonic cell types, such as the inhibitory effect of extraembryonic endoderm cells on the growth of pluripotent cells, and underscores the importance of intercellular communication during embryogenesis. The study also identifies common and unique factors involved in the regulation of extraembryonic endodermal stem cells in different species.
Dr. Wu noted, "This fundamental study of stem cell biology has the potential to provide important insights into the causes of congenital malformations and early developmental disorders. The insights derived from this study lay the foundation for potential preventive and therapeutic strategies for such disorders."
Yulei Wei, first author of the paper and a professor at the School of Biological Sciences, China Agricultural University, said, "Overall, the ability to mimic the natural embryonic environment in vitro could greatly advance the study of early human development and diseases, potentially leading to new therapeutic and preventive strategies."
Image from Cell, 2023, doi:10.1016/j.cell.2023.11.008.
These new findings build on earlier research efforts in Dr. Wu's lab, which contributed to basic and translational research to generate novel stem cells. Scientists have identified several novel pluripotent stem cells (PSC) from different species with distinct molecular and phenotypic profiles, and have generated PSC-derived interspecies chimeras and complementary systems of blastocysts for generating organs and tissues. Recently, Dr. Wu's team developed strategies to construct stem cell embryo models for in vitro studies of perinatal development.
In a study published in the journal Cell Stem Cell in 2021, Dr. Wu's lab devised a culture method to generate intermediate states of pluripotent stem cells from mouse and equine blastomeres (Cell Stem Cell, 2021, doi:10.1016/j.stem.2020.11.003). This new study found that the same culture conditions can be used to obtain embryonic stem cells and extraembryonic stem cells, such as trophoblast stem cells and extraembryonic endoderm stem cells, from mouse and primate blastomeres.
This new study furthers Dr. Wu's lab's research on the interactions between embryonic and extraembryonic tissues during early mammalian development using stem cell-based embryonic models. Previous studies have successfully developed stem cell models of the early mammalian embryo, including blastocyst-like structures (called blastocyst-like embryos) in mice, cows, and humans, as well as structures resembling the human peripheral proto-gastrulation (peri-gastrulation) (called human peripheral proto-gastrulation-like embryos).
These discoveries have the potential to impact research and therapeutic approaches for a range of disorders, particularly those diseases and areas related to (1) developmental disorders: understanding the coordinated relationship between embryonic and extra-embryonic tissues can shed light on congenital malformations and developmental disorders that occur during early embryonic development; (2) placental anomalies: an understanding of trophoblastic stem cells that contribute to the formation of the placenta could improve the understanding of placental abnormalities such as preeclampsia or placental abruption; (3) regenerative medicine: the ability to co-cultivate embryonic and extra-embryonic stem cells promotes the development of tissue engineering and organ organization, which may be beneficial for the treatment of diseases that require tissue regeneration; and (4) cancer research: since some cancers involve signaling pathways that are common to stem cell regulation, such as FGF, TGF-β, and WNT, the new study may help to understand tumor growth and development. study may contribute to the understanding of tumor growth and metastasis; (5) Reproductive health: this new study may improve the understanding of early embryonic development and implantation processes, thus advancing the development of fertility treatments.
