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Human primordial germ cells (hPGCs), the precursors of sperm and eggs, are specified during weeks 2-3 after fertilization. Few studies on ex vivo and in vitro cultured human embryos reported plausible hPGCs on embryonic day (E) 12-13 and in an E16-17 gastrulating embryo. In vitro, hPGC-like cells (hPGCLCs) can be specified from the intermediary pluripotent stage or peri-gastrulation precursors. Here, we explore the broad spectrum of hPGCLC precursors and how different precursors impact hPGCLC development. We show that resetting precursors can give rise to hPGCLCs (rhPGCLCs) in response to BMP. Strikingly, rhPGCLCs co-cultured with human hindgut organoids progress at a pace reminiscent of in vivo hPGC development, unlike those derived from peri-gastrulation precursors. Moreover, rhPGCLC specification depends on both EOMES and TBXT, not just on EOMES as for peri-gastrulation hPGCLCs. Importantly, our study provides the foundation for developing efficient in vitro models of human gametogenesis.
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http://dx.doi.org/10.1016/j.celrep.2022.111907 | DOI Listing |
Elife
August 2025
Department of Zoology, Graduate School of Science, Kyoto University Sakyo-ku, Kyoto, Japan.
The gut undergoes peristaltic movements regulated by intricate cellular interactions. How these interactions emerge in the developing gut remains poorly explored due to a lack of model system. We here developed a novel contractile organoid that is derived from the muscle layer of chicken embryonic hindgut.
View Article and Find Full Text PDFJ Clin Invest
August 2025
Section of Gastroenterology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Esophageal adenocarcinoma is increasingly prevalent and is thought to arise from Barrett's esophagus (BE), a metaplastic condition in which chronic acid and bile reflux transforms the esophageal squamous epithelium into a gastric-intestinal glandular mucosa. The molecular determinants driving this metaplasia are poorly understood. We developed a human BE organoid biobank that recapitulates BE's molecular heterogeneity.
View Article and Find Full Text PDFMicroPubl Biol
May 2025
Center for Stem Cell and Organoid Medicine (CuSTOM), Division of Developmental Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
The ability of transcription factors (TFs) to regulate cell fate decisions is paramount in developmental, homeostatic, and pathogenic contexts. The homeodomain TF NKX2-1 is an essential and evolutionarily conserved master regulator of pulmonary fate in vertebrates. In this study, we tested the spatial-temporal ability of Xenopus and Human NKX2-1 to respecify foregut and hindgut endoderm in developing embryos into a pulmonary fate, as indicated by expression of pulmonary surfactant genes and .
View Article and Find Full Text PDFiScience
May 2025
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
The cloaca is a transient structure that forms in the terminal hindgut giving rise to the rectum dorsally and the urogenital sinus ventrally. Similarly, human hindgut cultures derived from human pluripotent stem cells generate human colonic organoids (HCOs) which also contain co-developing urothelial tissue. In this study, our goal was to identify pathways involved in cloacal patterning and apply this to human hindgut cultures.
View Article and Find Full Text PDFiScience
March 2025
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Understanding how morphogen gradients spatially pattern tissues is a fundamental question in developmental biology but can be difficult to directly address using conventional approaches. Here, we expose hPSC-derived endoderm cells to countervailing gradients of anteriorizing and posteriorizing signals using a widely available microfluidic device. This approach yielded spatially patterned cultures comprising anterior foregut (precursor to the thyroid, esophagus, and lungs) and mid/hindgut (precursor to the intestines) cells, whose identities were confirmed using single-cell RNA sequencing (scRNA-seq).
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