Atoh7 is transiently expressed in retinal progenitor cells (RPCs) and is required for retinal ganglion cell (RGC) differentiation. In humans, a deletion in a distal non-coding regulatory region upstream of ATOH7 is associated with optic nerve atrophy and blindness. Here, we functionally interrogate the significance of the Atoh7 regulatory landscape to retinogenesis in mice.
View Article and Find Full Text PDFTherapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood.
View Article and Find Full Text PDFIn the developing vertebrate retina, retinal progenitor cells (RPCs) proliferate and give rise to terminally differentiated neurons with exquisite spatio-temporal precision. Lineage commitment, fate determination and terminal differentiation are controlled by intricate crosstalk between the genome and epigenome. Indeed, epigenetic regulation plays pivotal roles in numerous cell fate specification and differentiation events in the retina.
View Article and Find Full Text PDFOrganelles juxtaposition has been detected for decades, although only recently gained importance due to a pivotal role in the regulation of cellular processes dependent on membrane contact sites. Endoplasmic reticulum (ER) and mitochondria interaction is a prime example of organelles contact sites. Mitochondria-associated membranes (MAM) are proposed to harbor ER-mitochondria tether complexes, mainly when these organelles are less than 30 nm apart.
View Article and Find Full Text PDFMüller glia are specialized retinal cells with stem cell properties in fish and frogs but not in mammals. Current efforts to develop gene therapies to activate mammalian Müller glia for retinal repair will require safe and effective delivery strategies for recombinant adeno-associated viruses (AAVs), vectors of choice for clinical translation. Intravitreal and subretinal injections are currently used for AAV gene delivery in the eye, but less invasive methods efficiently targeting Müller glia have yet to be developed.
View Article and Find Full Text PDFHistone post-translational modification has been shown to play a pivotal role in regulating gene expression and fate determination during the development of the central nervous system. Application of pharmacological blockers that control histone methylation status has been considered a promising avenue to control abnormal developmental processes and diseases as well. In this study, we focused on the role of potent histone demethylase inhibitor GSK-J1 as a blocker of Jumonji domain-containing protein 3 (Jmjd3) in early postnatal retinal development.
View Article and Find Full Text PDFExtracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, participate in intercellular communication, and particularly, in paracrine and endocrine signalling. The EVs and their specific contents have been considered hallmarks of different diseases. It has been recently discovered that EVs can co-transport nucleic acids such as DNAs, ribosomal RNAs, circular RNAs (circRNAs), long noncoding RNAs (lnRNAs) and microRNAs (miRNAs).
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
February 2015
Purpose: Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide, and there is an urgent need to identify critical diagnostic and prognostic factors for early detection of the disease. Our aim in this study was to elucidate absolute copy number of SALL4 mRNA in the peripheral blood and serum of CRC patients to evaluate its probable prognostic or diagnostic value for CRC.
Methods: Peripheral mononuclear cells from 111 cases were examined using absolute quantitative real-time RT-PCR to assess the exact copy number of SALL4 and CEA mRNA.
Cancer cells have countless behaviors of pluripotent embryonic stem cells and germ line cells, such as unlimited proliferation, self-renewal, and migration. Expression of specific germ line and embryonic genes in tumor cells may be associated with indefinite growth and invasiveness of such cells. Developmental pluripotency factor 2 (DPPA2) and HIWI are two important developmental genes which are involved in embryonic and germ line stem cell properties.
View Article and Find Full Text PDFWnt signaling is an important evolutionary conserved pathway that is not only involved in determination of cellular development, self-renewal, and fate, but also has significant roles in tumor development and progression. Deregulation of the Wnt/β-catenin signaling pathway and aberrant expression of its components is commonly observed in solid tumors. Such aberrant regulation of Wnt signaling is commonly related to either malfunction of its components or crosstalk with other cellular processes such as the epidermal growth factor receptor (EGFR) signaling cascade.
View Article and Find Full Text PDFBackground: Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, self-renewal. A complex network of transcription factors and signaling molecules are required for continuance of this trait. SALL4 is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in colorectal tumor cells.
View Article and Find Full Text PDFThe use of unrestricted somatic stem cells (USSCs) holds great promise for future clinical applications. Conventionally, mouse embryonic fibroblasts (MEFs) or other animal-based feeder layers are used to support embryonic stem cell (ESC) growth; the use of such feeder cells increases the risk of retroviral and other pathogenic infection in clinical trials. Implementation of a human-based feeder layer, such as hUSSCs that are isolated from human sources, lowers such risks.
View Article and Find Full Text PDFBackground: Epithelial-mesenchymal transition has recently attracted great attention in studying the malignant progression of cells through a converging pathway of oncogenesis and metastasis. Twist1 and Mastermind-like 1 (MAML1) are major regulators of EMT through different pathways. The aim of this study was to investigate the clinicopathological relevance of the expression of MAML-1 and Twist1 genes in esophageal squamous cell carcinoma (ESCC).
View Article and Find Full Text PDFCancer-testis antigens (CTAs) are often specifically expressed in cancer cells and under normal conditions are only considered to be expressed in the germ line cells and the placenta. CTAs are potential targets for cancer immunotherapy and therefore necessitates their expression profiling. The expression profile of LAGE1, MAGE-A4 and NY-ESO1, their possible correlations and interaction, and the clinicopathological associations of each marker were studied.
View Article and Find Full Text PDFBackground: Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome.
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