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Differentiation; Research in Biological Diversity

Erica D Smith, Arturo G Garza-Gongora, Kyle L MacQuarrie, Steven T Kosak
The protein-DNA complexes that compose the end of mammalian chromosomes-telomeres-serve to stabilize linear genomic DNA and are involved in cellular and organismal aging. One mechanism that protects telomeres from premature degradation is the formation of structures called t-loops, in which the single-stranded 3' overhang present at the terminal end of telomeres loops back and invades medial double-stranded telomeric DNA. We identified looped structures formed between terminal chromosome ends and interstitial telomeric sequences (ITSs), which are found throughout the human genome, that we have termed interstitial telomeric loops (ITLs)...
June 18, 2018: Differentiation; Research in Biological Diversity
Emma A Fairhall, Alistair C Leitch, Anne F Lakey, Philip M E Probert, Gabriella Richardson, Carol De Santis, Matthew C Wright
The rodent pancreatic AR42J-B13 (B-13) cell line differentiates into non-replicative hepatocyte-like cells in response to glucocorticoid mediated via the glucocorticoid receptor (GR). The aims of this study were to identify a human cell line that responds similarly and investigate the mechanisms underpinning any alteration in differentiation. Exposing the human pancreatic adenocarcinoma (HPAC) cell line to 1-10 µM concentrations of dexamethasone (DEX) resulted an inhibition of proliferation, suppressed carcinoembryonic antigen expression, limited expression of pancreatic acinar and hepatic gene expression and significant induction of the constitutively-expressed hepatic CYP3A5 mRNA transcript...
May 22, 2018: Differentiation; Research in Biological Diversity
Yuefang Zhou, Alan Shiels
Ephrin type-A receptor 2 (EPHA2) and one of its ligands, ephrin-A5 (EFNA5), have been associated with loss of eye lens transparency, or cataract, - an important cause of visual impairment. Here we show that mice functionally lacking EPHA2 (Epha2-null), EFNA5 (Efna5-null), or both receptor and ligand (Epha2/Efna5-null) consistently develop mostly transparent lenses with an internal refractive disturbance and a grossly disturbed cellular architecture. In situ hybridization localized Epha2 and Efna5 transcripts to lens epithelial cells and nascent fiber cells at the lens equator...
May 17, 2018: Differentiation; Research in Biological Diversity
Ge Liu, Xin Liu, Joel Shen, Adriane Sinclair, Laurence Baskin, Gerald R Cunha
This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle...
May 2018: Differentiation; Research in Biological Diversity
Gerald R Cunha, Takeshi Kurita, Mei Cao, Joel Shen, Paul S Cooke, Stanley J Robboy, Laurence S Baskin
The role of tissue interactions was explored to determine whether epithelial differentiation within the developing human reproductive tract is induced and specified by mesenchyme in tissue recombinants composed of mouse vaginal mesenchyme + human uterine tubal epithelium (mVgM+hTubE). The tissue recombinants were grown in DES-treated ovariectomized athymic mice. After 2-4 weeks of in vivo growth, several vaginal specific features were expressed in the human tubal epithelium. The mesenchyme-induced effects included morphological change as well as expression of several immunohistochemical markers...
May 2018: Differentiation; Research in Biological Diversity
Amilton Cesar Dos Santos, Alan James Conley, Moacir Franco de Oliveira, Antônio Chaves de Assis Neto
This study documented, for the first time, the morphological patterns of differentiation of male and female genital organs of Spix cavy (Galea spixii) using histological and ultrastructural analyses, with immuno-localization of steroidogenic enzymes, cytochromes P450 aromatase (P450arom) and 17α-hydroxylase/17, 20-lyase (P450c17), involved in the synthesis of estrogens and androgens respectively throughout fetal sexual development. Undifferentiated gonads of Spix cavy develop into ovaries in females after 25 days of gestation (DG), exhibiting P450arom immunoreactivity...
May 2018: Differentiation; Research in Biological Diversity
Faizal Z Asumda, Konstantinos E Hatzistergos, Derek M Dykxhoorn, Silvia Jakubski, Jasmine Edwards, Emmanuel Thomas, Eugene R Schiff
A variety of approaches have been developed for the derivation of hepatocyte-like cells from pluripotent stem cells. Currently, most of these strategies employ step-wise differentiation approaches with recombinant growth-factors or small-molecule analogs to recapitulate developmental signaling pathways. Here, we tested the efficacy of a small-molecule based differentiation protocol for the generation of hepatocyte-like cells from human pluripotent stem cells. Quantitative gene-expression, immunohistochemical, and western blot analyses for SOX17, FOXA2, CXCR4, HNF4A, AFP, indicated the stage-specific differentiation into definitive endoderm, hepatoblast and hepatocyte-like derivatives...
May 2018: Differentiation; Research in Biological Diversity
Fereshteh Karamali, Mohammad-Hossein Nasr Esfahani, Sara Taleahmad, Leila Satarian, Hossein Baharvand
Recently, we have found that human stem cells from apical papilla (SCAP) show a stromal cell-derived inducing activity (SDIA). To examine SDIA competence for retinal cells differentiation, we co-cultured SCAP with human pluripotent stem cells (hPSCs). In comparison with Matrigel-cultured hPSCs, SCAP significantly induces hPSCs to differentiate into rostral neural cells as demonstrated by upregulation of OTX2 and PAX6 and down-regulation of EN1, HOXB4 and HOXC8. Furthermore, the differentiated cells on SCAP significantly expressed eye-field markers, RAX, PAX6, LHX2 and SIX3 and showed five folds pigmented colonies...
May 2018: Differentiation; Research in Biological Diversity
Jung-Il Jung, Kyeong-Yong Park, Yura Lee, Mira Park, Jiyeon Kim
Vitamin C-linker-conjugated Ala-His-Lys tripeptide (Vit C-AHK) is a derivative of Vitamin C-conjugated tripeptides, which were originally developed as a component of a product for collagen synthesis enhancement or human dermal fibroblast growth. Here, we investigated the effect of Vit C-AHK on bone morphogenetic protein (BMP)-2-induced osteoblast differentiation in a cell culture model. Vit C-AHK enhanced proliferation of C2C12 cells and induction of BMP-2-induced alkaline phosphatase, a typical marker of osteoblast differentiation...
May 2018: Differentiation; Research in Biological Diversity
Rafal P Piprek, Milena Damulewicz, Malgorzata Kloc, Jacek Z Kubiak
Development of the gonads is a complex process, which starts with a period of undifferentiated, bipotential gonads. During this period the expression of sex-determining genes is initiated. Sex determination is a process triggering differentiation of the gonads into the testis or ovary. Sex determination period is followed by sexual differentiation, i.e. appearance of the first testis- and ovary-specific features. In Xenopus laevis W-linked DM-domain gene (DM-W) had been described as a master determinant of the gonadal female sex...
March 2018: Differentiation; Research in Biological Diversity
Stefano Misino, Diego Bonetti, Sarah Luke-Glaser, Brian Luke
Cancer cells activate telomere maintenance mechanisms (TMMs) to bypass replicative senescence and achieve immortality by either upregulating telomerase or promoting homology-directed repair (HDR) at chromosome ends to maintain telomere length, the latter being referred to as ALT (Alternative Lengthening of Telomeres). In yeast telomerase mutants, the HDR-based repair of telomeres leads to the generation of 'survivors' that escape senescence and divide indefinitely. So far, yeast has proven to provide an accurate model to study the generation and maintenance of telomeres via HDR...
March 2018: Differentiation; Research in Biological Diversity
Alex C Y Chang, Helen M Blau
Cardiovascular diseases are the leading cause of death worldwide and the incidence increases with age. Genetic testing has taught us much about the pathogenic pathways that drive heritable cardiomyopathies. Here we discuss an unexpected link between shortened telomeres, a molecular marker of aging, and genetic cardiomyopathy. Positioned at the ends of chromosomes, telomeres are DNA repeats which serve as protective caps that shorten with each cell division in proliferative tissues. Cardiomyocytes are an anomaly, as they are largely non-proliferative post-birth and retain relatively stable telomere lengths throughout life in healthy individuals...
March 2018: Differentiation; Research in Biological Diversity
Esther Aix, Alex Gallinat, Ignacio Flores
Although recent advances have overturned the old view of the human heart as an inert postmitotic organ, it is clear that the adult heart´s capacity to regenerate after an ischemic episode is very limited. Unlike humans, zebrafish and other lower vertebrates vigorously regenerate damaged myocardium after cardiac injury. Understanding how the zebrafish is able to conserve life-long cardiac regeneration capacity while mammals lose it soon after birth is crucial for the development of new treatments for myocardial infarction...
March 2018: Differentiation; Research in Biological Diversity
Julia Su Zhou Li, Eros Lazzerini Denchi
In multicellular organisms, regulation of telomere length in pluripotent stem cells is critical to ensure organism development and survival. Telomeres consist of repetitive DNA that are progressively lost with each cellular division. When telomeres become critically short, they activate a DNA damage response that results in cell cycle arrest. To counteract telomere attrition, pluripotent stem cells are equipped with telomere elongation mechanisms that ensure prolonged proliferation capacity and self-renewal capacity...
March 2018: Differentiation; Research in Biological Diversity
Haitong Hou, Julia Promisel Cooper
The consequences of telomere loss or dysfunction become most prominent when cells enter the nuclear division stage of the cell cycle. At this climactic stage when chromosome segregation occurs, telomere fusions or entanglements can lead to chromosome breakage, wreaking havoc on genome stability. Here we review recent progress in understanding the mechanisms of detangling and breaking telomere associations at mitosis, as well as the unique ways in which telomeres are processed to allow regulated sister telomere separation...
March 2018: Differentiation; Research in Biological Diversity
Elena Fiorini, Andrea Santoni, Simona Colla
Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation...
March 2018: Differentiation; Research in Biological Diversity
Heather L Mentrup, Amanda Hartman, Elizabeth L Thames, Wassim A Basheer, Lydia E Matesic
Maintenance of the intestinal mucosa is driven by local signals that coordinate epithelial proliferation, differentiation, and turnover in order to separate antigenic luminal contents from the host's immune system. Breaches in this barrier promote gastrointestinal pathologies ranging from inflammatory bowel disease to cancer. The ubiquitin ligase ITCH is known to regulate immune responses, and loss of function of ITCH has been associated with gastrointestinal inflammatory disorders, particularly in the colon...
January 2018: Differentiation; Research in Biological Diversity
Cagatay Gunes, Alush Irene Avila, K Lenhard Rudolph
Telomere shortening as a consequence of cell divisions during aging and chronic diseases associates with an increased cancer risk. Experimental data revealed that telomere shortening results in telomere dysfunction, which in turn affects tumorigenesis in two ways. First, telomere dysfunction suppresses tumor progression by the activation of DNA damage checkpoints, which induce cell cycle arrest (senescence) or apoptosis, as well as by inducing metabolic compromise and activation of immune responses directed against senescent cells...
January 2018: Differentiation; Research in Biological Diversity
Zhe Wang, Yukiko Nakayama, Sachiko Tsuda, Kyo Yamasu
During vertebrate brain development, the gastrulation brain homeobox 2 gene (gbx2) is expressed in the forebrain, but its precise roles are still unknown. In this study, we addressed this issue in zebrafish (Danio rerio) first by carefully examining gbx2 expression in the developing forebrain. We showed that gbx2 was expressed in the telencephalon during late somitogenesis, from 18h post-fertilization (hpf) to 24 hpf, and in the thalamic primordium after 26 hpf. In contrast, another gbx gene, gbx1, was expressed in the anterior-most ventral telencephalon after 36 hpf...
January 2018: Differentiation; Research in Biological Diversity
Wareed Ahmed, Joachim Lingner
Telomere integrity is essential for genome stability and it regulates cell proliferation and tissue renewal. Several lines of evidence indicate that telomeres are particularly sensitive to oxidative damage. Moreover, recent studies demonstrate striking inhibitory effects of oxidative damage on telomerase activity. On the other hand, several mechanisms have been uncovered that either counteract oxidative damage at telomeres or remove the modified lesions. Here, we review the current understanding of oxidative damage and protection of telomeric DNA...
January 2018: Differentiation; Research in Biological Diversity
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