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https://www.readbyqxmd.com/read/29423528/cellular-functions-of-stem-cell-factors-mediated-by-the-ubiquitin-proteasome-system
#1
REVIEW
Jihye Choi, Kwang-Hyun Baek
Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin-proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery...
February 8, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29416635/otud7b-upregulation-predicts-a-poor-response-to-paclitaxel-in-patients-with-triple-negative-breast-cancer
#2
Hui-Wen Chiu, Hui-Yu Lin, Ing-Jy Tseng, Yuan-Feng Lin
Paclitaxel is a first-line chemotherapeutic for patients with breast cancer, particularly triple-negative breast cancer (TNBC). Molecular markers for predicting pathologic responses to paclitaxel treatment is thus urgently needed since paclitaxel resistance is still a clinical issue in treating TNBCs. We investigated the transcriptional profiling of consensus genes in HCC38 (paclitaxel-sensitive) and MDA-MB436 (paclitaxel-resistant) TNBC cells post-treatment with paclitaxel. We found that OTUD7B was downregulated in HCC38 but upregulated in MDA-MB436 cells after paclitaxel treatment at cytotoxic concentrations...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29393461/lin28-microrna-let-7a-promotes-metastasis-under-circumstances-of-hyperactive-wnt-signaling-in-esophageal-squamous-cell-carcinoma
#3
Rui Ling, Yuepeng Zhou, Ling Zhou, Dongfang Dai, Dan Wu, Lei Mi, Chaoming Mao, Deyu Chen
Dysregulation of micro (mi)RNA-let-7 has been associated with the development and prognosis of multiple cancer types. Lin28, a RNA-binding protein, plays a conserved role in regulating the maturation of let-7 family proteins. However, few studies have focused on the effects of Lin28/let-7 on Wnt-activated esophageal squamous cell carcinoma (ESCC). Analysis of the expression of let-7a, let-7b and let-7c in clinical tissues revealed that lower let-7a expression was correlated with higher tumor node metastasis staging and recurrence in patients with ESCC...
February 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29393430/silencing-lin28-promotes-apoptosis-in-colorectal-cancer-cells-by-upregulating-let%C3%A2-7c-targeting-of-antiapoptotic-bcl2l1
#4
Haogang Zhang, Yaguang Zong, Gongcai Qiu, Ruichun Jia, Xunzheng Xu, Fujing Wang, Dequan Wu
Colorectal cancer (CRC) remains a primary contributor to cancer‑associated mortality. The Lin28/let‑7 axis has previously been verified to participate in numerous pathophysiological processes involved in CRC. However, the potential roles and underlying mechanisms of this axis in apoptosis during CRC remain to be fully elucidated. The present study aimed to evaluate the role and reveal the molecular mechanisms of the Lin28/let‑7 axis in the apoptosis of CRC cells. An MTT assay was conducted to assess the cell viability of HCT116 and HT29 CRC cells, and caspase‑3 activity was analyzed to measure the apoptosis of CRC cells...
January 25, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29380422/microrna-31-is-required-for-astrocyte-specification
#5
Gordon P Meares, Rajani Rajbhandari, Magda Gerigk, Chih-Liang Tien, Chenbei Chang, Samuel C Fehling, Amber Rowse, Kayln C Mulhern, Sindhu Nair, G Kenneth Gray, Nicolas F Berbari, Markus Bredel, Etty N Benveniste, Susan E Nozell
Previously, we determined microRNA-31 (miR-31) is a noncoding tumor suppressive gene frequently deleted in glioblastoma (GBM); miR-31 suppresses tumor growth, in part, by limiting the activity of NF-κB. Herein, we expand our previous studies by characterizing the role of miR-31 during neural precursor cell (NPC) to astrocyte differentiation. We demonstrate that miR-31 expression and activity is suppressed in NPCs by stem cell factors such as Lin28, c-Myc, SOX2 and Oct4. However, during astrocytogenesis, miR-31 is induced by STAT3 and SMAD1/5/8, which mediate astrocyte differentiation...
January 30, 2018: Glia
https://www.readbyqxmd.com/read/29378863/notch-suppression-collaborates-with-ascl1-and-lin28-to-unleash-a-regenerative-response-in-fish-retina-but-not-in-mice
#6
Fairouz Elsaeidi, Peter Macpherson, Elizabeth A Mills, Jonathan Jui, John G Flannery, Daniel Goldman
Muller glial cells (MG) in the zebrafish retina respond to injury by acquiring retinal stem cell characteristics. Thousands of gene expression changes are associated with this event. Key among these changes are the induction of Ascl1a and Lin28a, two reprogramming factors whose expression is necessary for retina regeneration. Whether these factors are sufficient to drive MG proliferation and subsequent neuronal-fate specification remains unknown. To test this, we conditionally expressed Ascl1a and Lin28a in the uninjured retina of male and female fish...
January 29, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29372665/dna-methylation-of-the-oct4a-enhancers-in-embryonal-carcinoma-cells-after-etoposide-treatment-is-associated-with-alternative-splicing-and-altered-pluripotency-in-reversibly-senescent-cells
#7
Mikhail Baryshev, Inna Inashkina, Kristine Salmina, Anda Huna, Thomas R Jackson, Jekaterina Erenpreisa
The epigenetic mechanisms underlying chemoresistance in cancer cells resulting from drug-induced reversible senescence are poorly understood. Chemoresistant ESC-like embryonal carcinoma PA1 cells treated with etoposide (ETO) were previously found to undergo prolonged G2 arrest with transient p53-dependent upregulation of opposing fate regulators, p21CIP1 (senescence) and OCT4A (self-renewal). Here we report on the analysis of the DNA methylation state of the distal enhancer (DE) and proximal enhancer (PE) of the Oct4A gene during this dual response...
January 26, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29336272/let-7-mirna-precursors-co-express-with-lin28b-in-cervical-cells
#8
Alvarez-Salas, Zamora-Contreras
BACKGROUND: The let-7 microRNAs (miRNAs) are frequently dysregulated in carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7 biogenesis by binding to conserved sequences within the pre-miRNA structure. Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28 regulation. OBJECTIVE: Correlate pre-let-7 miRNAs and LIN28B levels in cervical cell lines with different malignancy and HPV content. METHODS: Pre-let-7 levels were determined by RTqPCR...
January 15, 2018: MicroRNA
https://www.readbyqxmd.com/read/29274886/establishment-of-human-ipsc-line-nccsi003-a-from-cd34-cells-of-peripheral-blood-collected-during-apheresis-of-healthy-donor-from-indian-ethnicity
#9
Sophia Fernandes, Shruti Tembe, Prajakta Shinde, Sameer Melinkeri, Vaijayanti Kale, Lalita Limaye
We present generation of iPSCs from CD34+ cells isolated from peripheral blood, collected during apheresis of a healthy female individual. We nucleofected the CD34+cells by episomal vectors containing Oct4, Sox2, L-Myc, Lin28, Klf4 and p53DD (dominant negative mutation in p53). The resultant colonies showed cobble-stone appearance and stained positive for alkaline phosphatase. The colonies demonstrated presence of pluripotency markers by immunofluorescence, flow-cytometry and PCR. The plasmids were lost from cells subsequently during passages as assessed by PCR...
December 20, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29259864/an-up-date-on-epigenetic-and-molecular-markers-in-testicular-germ-cell-tumors
#10
Paolo Chieffi
Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. Clinically several types of immunohistochemical markers are useful and sensitive. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include OCT3/4, HMGA1 and 2, NANOG, SOX2, and LIN28. Gene expression in TGCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation...
November 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/29250763/transplantation-of-spermatogonial-stem-cells-suspension-into-rete-testis-of-azoospermia-mouse-model
#11
Arefeh Jafarian, Niknam Lakpour, Mohammad Reza Sadeghi, Sheida Salehkhou, Mohammad Mehdi Akhondi
PURPOSE: The loss of spermatogonia following chemo-or radiotherapy leading to temporary or permanent infertility of the patient is a well known and unwanted side effect of many oncological therapies. MATERIALS AND METHODS: In this study, germ cells were isolated from 4 days old mouse testis cells. Busulfan treatment was used to the eliminate proliferating cells in the testis of recipient mice. The donor cells suspended in DMEM, were introduced into the rete testis of recipient mice via microinjection method...
December 17, 2017: Urology Journal
https://www.readbyqxmd.com/read/29246570/integration-free-induced-pluripotent-stem-cells-derived-from-a-patient-with-autosomal-recessive-alport-syndrome-aras
#12
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
A skin biopsy was obtained from a 25-year-old female patient with autosomal recessive Alport syndrome (ARAS) with the homozygous COL4A3 mutation c.345delG, p.(P166Lfs*37). Dermal fibroblasts were derived and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53shRNA. The generated induced Pluripotent Stem Cell (iPSC) clone AS FiPS1 Ep6F-2 was free of genomically integrated reprogramming genes, had the specific homozygous mutation, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
December 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29218439/characterization-and-expression-of-lin-28a-involved-in-lin28-let-7signal-pathway-during-early-development-of-p-olivaceus
#13
Yuanshuai Fu, Lina Gao, Zhiyi Shi, Feng You, Junling Zhang, Wenjuan Li
Heterochronic lin-28 is a conserved RNA-binding protein that plays a key role in the timing of developmental events in organisms. As a crucial heterochronic gene, the protein controls developmental events of the second of four larval stages in Caenorhabditi elegans. Heterochronic let-7 miRNAs are often present in various species and highly conserved in sequence and biological function and are required for various biological processes. Previous studies showed that ten let-7 miRNAs were identified in the Japanese flounder (Paralichthys olivaceus) and that they were primarily expressed during metamorphosis...
December 7, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#14
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29201231/genetic-variation-of-rs3811463-is-associated-with-gestational-diabetes-mellitus-susceptibility
#15
Yun Liu, Zhi-Ping Ge, Li-Zhou Sun, Pei Tong, Hong-Mei Lu
Gestational diabetes mellitus (GDM) is a growing health concern, and it increases the risk of adverse pregnancy outcomes with substantial long-term adverse health impacts on mothers and their offspring. Several studies have revealed specific associations between genetic variants and the risk of GDM. Single nucleotide polymorphisms (SNPs) are the major type of genetic variation in humans. Let-7 microRNA targets are enriched for genes containing SNPs associated with glucose metabolism, including Lin28. In the present study, the effect of T/C variants of rs3811463 (a SNP located near to the let-7 binding site in Lin28) on GDM risk was investigated...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29163026/generation-of-urine-cell-derived-non-integrative-human-ipscs-and-inscs-a-step-by-step-optimized-protocol
#16
Lin Cheng, Qiannan Lei, Chen Yin, Hui-Yun Wang, Kangxin Jin, Mengqing Xiang
Objective: Establishing a practical procedure to generate induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) from human urine cells (UCs). In this report, we optimized a non-integrative protocol to generate patient-specific iPSC and iNSC lines with high reprogramming efficiency. Methods: UCs were electroporated with the pEP4-EO2S-ET2K and pEP4-M2L plasmids containing the OCT4, SOX2, KLF4, SV40LT, c-MYC, and LIN28 genes, and then cultured with N2B27 medium plus four small molecule compounds (A83-01, PD0325901, Thiazovivin, and CHIR99021)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162857/temporal-expression-pattern-of-genes-during-the-period-of-sex-differentiation-in-human-embryonic-gonads
#17
Linn S Mamsen, Emil H Ernst, Rehannah Borup, Agnete Larsen, Rasmus H Olesen, Erik Ernst, Richard A Anderson, Stine G Kristensen, Claus Y Andersen
The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry (IHC). SRY/SOX9 expression initiated in testis around day 40 pc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1 was significantly higher in testis than ovaries...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150092/generation-of-integration-free-induced-pluripotent-stem-cell-lines-derived-from-two-patients-with-x-linked-alport-syndrome-xlas
#18
Bernd Kuebler, Begoña Aran, Laia Miquel-Serra, Yolanda Muñoz, Elisabet Ars, Gemma Bullich, Monica Furlano, Roser Torra, Merce Marti, Anna Veiga, Angel Raya
Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro...
September 9, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29092089/notch-wnt-cross-signalling-regulates-stemness-of-dental-pulp-stem-cells-through-expression-of-neural-crest-and-core-pluripotency-factors
#19
V Uribe-Etxebarria, J Luzuriaga, P García-Gallastegui, A Agliano, F Unda, G Ibarretxe
Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal...
November 1, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/29034895/generation-of-induced-pluripotent-stem-cell-ipsc-line-from-charcot-marie-tooth-disease-patient-with-mpz-mutation-cmt1b
#20
Daryeon Son, Phil Jun Kang, Wonjin Yun, Seungkwon You
Charcot-Marie-Tooth disease (CMT1B) is an inherited neurological disorder caused by mutation of the myelin protein zero (MPZ) gene. We generated an induced pluripotent stem cell (iPSC) line from an 81-year-old patient with CMT1B by electroporating of lymphoblastoid cell lines with episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, LIN28, and p53-targeting shRNA. The established iPSCs expressed various pluripotency markers, demonstrated the potential to differentiate into cells of the three germ layers in vitro, had a normal karyotype and retained the MPZ mutation...
October 2017: Stem Cell Research
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