The preimplantation mammalian embryo is a simplistic, self-contained, and a superior model for investigating the inherent complexities of cell fate decision mechanisms. All mammals begin their humble journey from a single-cell fertilized zygote contained within a proteinaceous coat called the zona pellucida. The zygote embarks on a series of well-orchestrated events, beginning with the activation of embryonic genome, transition from meiotic to mitotic divisions, spatial organization of the cells, timely differentiation into committed trophectoderm (TE) and primitive endoderm (PrE), and ultimately escape from zona pellucida for implantation into the uterus. The entire development of preimplantation embryo can be studied in vitro using a minimalistic and defined culture system. The ease of culture along with the ability to manipulate gene expression and image the embryos makes them an ideal model system for investigation into the first two of several cell fate decisions made by the embryo that result in a pluripotent epiblast (EPI) and differentiated TE and PrE lineages. This chapter reviews our latest knowledge of preimplantation embryo development, setting the stage for understanding placental development in subsequent chapters in this Book.
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http://dx.doi.org/10.1007/978-3-030-77360-1_3 | DOI Listing |
Exp Hematol
March 2025
Institute of Regenerative Medicine, and Department of Dermatology, Affiliated Hospital of Jiangsu University, Jiangsu University, 212001 Zhenjiang, Jiangsu, China; Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Chinese Academy of Medical Sciences, 300020 Tianjin, China; Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, and South China Institute of Large Animal Models for Biomedicine, School of Pharmacy and Food Engineering, Wuyi University, 529020 Jiangmen, Guangdong, China; Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Medicinal and Life Sciences, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan. Electronic address:
Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogen, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges.
View Article and Find Full Text PDFStem Cell Reports
February 2025
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510060, China. Electronic address:
Proper development of surface epithelium (SE) is a requisite for the normal development and function of ectodermal appendages; however, the molecular mechanisms underlying SE commitment remain largely unexplored. Here, we developed a KRT8 reporter system and utilized it to identify FOXO4 and SP6 as novel, essential regulators governing SE commitment. We found that the FOXO4-SP6 axis governs SE fate and its abrogation markedly impedes SE fate determination.
View Article and Find Full Text PDFCancer Cell
March 2025
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:
The abscopal effect of radioimmunotherapy, wherein tumor shrinkage occurs beyond the irradiated field, is therapeutically promising but clinically rare. The mechanisms underlying this effect remain elusive. Here, in vivo genome-wide CRISPR screening identifies SFRP2 as a potential stromal regulator of the abscopal effect.
View Article and Find Full Text PDFCell Syst
March 2025
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:
Direct conversion generates patient-specific, disease-relevant cell types, such as neurons, that are rare, limited, or difficult to isolate from common and easily accessible cells, such as skin cells. However, low rates of direct conversion and complex protocols limit scalability and, thus, the potential of cell-fate conversion for biomedical applications. Here, we optimize the conversion protocol by examining process parameters, including transcript design; delivery via adeno-associated virus (AAV), retrovirus, and lentivirus; cell seeding density; and the impact of media conditions.
View Article and Find Full Text PDFCell Syst
March 2025
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:
The sparse and stochastic nature of conversion has obscured our understanding of how transcription factors (TFs) drive cells to new identities. To overcome this limit, we develop a tailored, high-efficiency conversion system that increases the direct conversion of fibroblasts to motor neurons 100-fold. By tailoring the cocktail to a minimal set of transcripts, we reduce extrinsic variation, allowing us to examine how proliferation and TFs synergistically drive conversion.
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