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Secreted effectors of the innate mucosal barrier
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Michael A. McGuckin, Andre J. Ouellette, Gary D. Wu
The Wnt pathway regulates cellular differentiation of the intestinal epithelium in several ways. First, the β-catenin/TCF transcriptional complex activates genes expressing Ephrin-B ligands and their receptors EphB, which have a role in establishing migratory pathways as well as maintaining cellular boundaries. The gradient of EphB receptor expression within the crypt maintains the correct cellular architecture with CBCs and Paneth cells located at the base of the crypt compartment. Deletion of EphB3 results in aberrant Paneth cell localization. Second, signaling through the Wnt pathway is required for Paneth cell maturation and their expression of antimicrobial peptides. Furthermore, the Wnt-dependent SOX9 gene is critical for Paneth cell development, because mice with a conditional deletion of Sox9 lack Paneth cells completely. Finally, Wnt signaling may have an effect on cell fate determination by impeding terminal differentiation of secretory cell lineages. TCF4−/− mice have goblet cells and enterocytes but lack enteroendocrine cells, whereas transgenic overexpression of Dkk1, an inhibitor of Wnt signaling, ablates the secretory cell lineages while absorptive enterocytes remain normal.
Human Liver Stem Cells:
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Another important emerging family, especially in bile duct development and morphogenesis is the Notch ligand/receptor system. Both receptor and ligand family members are large molecular weight membrane-spanning proteins, indicating that biological activation is restricted to cells in immediate contact with one another. First described in Drosophila77 the Jagged Notch pathway regulates cell fate determination during development. In eukaryotes their properties are still being defined, but it is known they act as key players in, for example, the regulation of early mammalian hematopoiesis78 and angiogenesis.79
Estrogens, Xenoestrogens, and the Development of Neoplasms
Published in Rajesh K. Naz, Endocrine Disruptors, 2004
Recently, the expression of some of these developmental genes was shown to oscillate in response to changes in circulating levels of steroid hormones during the murine estrous cycle, or down-regulate following ovariectomy. Therefore, the subsequent findings that prenatal exposure to the potent estrogen DES altered the expression of Wnt 7a and Hoxa-10 during uterine morphogenesis in the mouse established an important correlation between chemical exposure and the ensuing developmental abnormalities associated with endocrine disruption.43,44,45 This link was made even more credible when the phenotype of mice carrying specific Hox and Wnt null mutations was observed to be strikingly similar to that of human and mouse “DES daughters.” The Wnt genes are associated with cellular responses such as cell proliferation, apoptosis, and cell-cell communication (through the β-catenin/E-cadherin complex). Changing patterns of expression due to environmental chemical exposure can thus provide insight into how these chemicals influence cell fate determination and tissue morphogenesis in hormone-sensitive organs.
Development of an adverse outcome pathway for radiation-induced microcephaly via expert consultation and machine learning
Published in International Journal of Radiation Biology, 2022
Thomas Jaylet, Roel Quintens, Mohamed Abderrafi Benotmane, Jukka Luukkonen, Ignacia Braga Tanaka, Chrystelle Ibanez, Christelle Durand, Magdalini Sachana, Omid Azimzadeh, Christelle Adam-Guillermin, Knut Erik Tollefsen, Olivier Laurent, Karine Audouze, Olivier Armant
Beside apoptosis, mitotic spindle defects (Shimada et al. 2016) and endoplasmic reticulum stress (Passemard et al. 2019) were also implicated in microcephaly in the context of IR exposure. Finally, data showed that TP53 have also a role in cell-fate determination during neurogenesis, independent of its classical function in the induction of apoptosis. Indeed, in vivo study using Trp53 mutant mice demonstrated that Trp53 hyperactivation led to a precocious differentiation of RGC into neurons during embryonic development (Liu et al. 2013; Mfossa et al. 2020). In this case, the pool of RGC is depleted too early (Gruber et al. 2011), limiting the production of neurons throughout neurogenesis and thereby contributing to a decreased brain size. Given all these data, the WG considered TP53 activation as a genuine KE essential for the appearance of microcephaly via two independent KE, namely apoptosis and premature neuronal differentiation.
MicroRNA-217: a therapeutic and diagnostic tumor marker
Published in Expert Review of Molecular Diagnostics, 2022
Amir Abbas Hamidi, Malihe Zangoue, Daniel Kashani, Amir Sadra Zangouei, Hamid Reza Rahimi, Mohammad Reza Abbaszadegan, Meysam Moghbeli
Dachshund homolog 1 (DACH1) is a developmental transcription factor involved in tumor progression [79]. As a cell-fate determination factor, the DACH1 gene can control normal development [80,81]. It has been shown that there were significant HOTAIR up regulations in NSCLC cell lines. Moreover, HOTAIR knockdown noticeably inhibited the migration, invasion, and growth of cancer cells. MiR-217 can suppress the proliferation, migration, and invasion of NSCLC cells through DACH1 down regulation [82]. Cyclin D1 (CCND1) regulates the G1-to-S phase during cell cycle progression by stimulating cyclin-dependent kinase 4/6 (CDK4/6) [83,84]. Cyclin D1-CDK4/6 complex phosphorylates the crucial substrates sequentially and facilitates the initiation of DNA replication in cells [85]. There was miR-217 up regulation in breast cancer (BC) that was associated with a poor prognosis. Moreover, miR-217 can directly suppress the DACH1 and enhance the cell cycle progression in BC by CCND1 up regulation [36]. Hepatocyte nuclear factor-1beta (HNF1β) is a liver-specific homeobox transcription factor that acts either as a homodimer or heterodimer with hepatocyte nuclear factor 1α (HNF1α) [86]. Derlin-1 is involved in the dislocation of misfolded ER-derived proteins and suppresses ER stress-induced cell death in tumor cells. It induces PI3K/AKT and ERK cascades [87,88]. It has been reported that there were circ-TTBK2 up regulations in glioma tissues and cell lines. It induces malignant progression of glioma cells through regulation of miR-217/HNF1β/ Derlin-1 axis [89].
Spatial profiling technologies and applications for brain cancers
Published in Expert Review of Molecular Diagnostics, 2021
Priyakshi Kalita-de Croft, Habib Sadeghi Rad, Harry Gasper, Ken O’Byrne, Sunil R Lakhani, Arutha Kulasinghe
Multiplexed error-robust fluorescence in situ hybridization (MERFISH) is a technique which uses direct imaging of individual RNA molecules in single cells. It utilizes the assignment of error-robust barcodes to individual RNA species followed by the labeling of RNA molecules with oligonucleotides representing each barcode and sequential single-molecule FISH imaging to read out these barcodes [58–60]. This not only provides quantitative measurements of RNA expression but also determines the spatial localization of individual RNAs on freshly frozen tissues, making it highly accurate and has a high detection efficiency [58,61]. These characteristics have led to new perspectives on biological processes, such as the establishment of cell polarity, cell migration, cell fate determination during cell division, and local translation [62]. Thus, using this technology, mapping, counting, and simultaneous imaging of thousands of RNA species in single cells are plausible, as well as enabling the delineation of regulatory networks and the in situ identification of cell types. However, currently, this is limited to 1001 mRNA molecules [58].