keyword
https://read.qxmd.com/read/38418821/hypoxia-induced-immortalization-of-primary-cells-depends-on-tfcp2l1-expression
#21
JOURNAL ARTICLE
D Otero-Albiol, J M Santos-Pereira, A Lucena-Cacace, C Clemente-González, S Muñoz-Galvan, Y Yoshida, A Carnero
Cellular senescence is a stress response mechanism that induces proliferative arrest. Hypoxia can bypass senescence and extend the lifespan of primary cells, mainly by decreasing oxidative damage. However, how hypoxia promotes these effects prior to malignant transformation is unknown. Here we observed that the lifespan of mouse embryonic fibroblasts (MEFs) is increased when they are cultured in hypoxia by reducing the expression of p16INK4a , p15INK4b and p21Cip1 . We found that proliferating MEFs in hypoxia overexpress Tfcp2l1, which is a main regulator of pluripotency and self-renewal in embryonic stem cells, as well as stemness genes including Oct3/4, Sox2 and Nanog...
February 28, 2024: Cell Death & Disease
https://read.qxmd.com/read/38418798/role-of-hydroxymethylglutharyl-coenzyme-a-reductase-in-the-induction-of-stem-like-states-in-breast-cancer
#22
JOURNAL ARTICLE
María Paula Marks, Carla Alejandra Giménez, Luciana Isaja, Mariana Belén Vera, Francisco Raúl Borzone, Federico Pereyra-Bonnet, Leonardo Romorini, Guillermo Agustín Videla-Richardson, Norma Alejandra Chasseing, Juan Carlos Calvo, Luciano Vellón
PURPOSE: De novo synthesis of cholesterol and its rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR), is deregulated in tumors and critical for tumor cell survival and proliferation. However, the role of HMGCR in the induction and maintenance of stem-like states in tumors remains unclear. METHODS: A compiled public database from breast cancer (BC) patients was analyzed with the web application SurvExpress. Cell Miner was used for the analysis of HMGCR expression and statin sensitivity of the NCI-60 cell lines panel...
February 28, 2024: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/38408774/interlinked-bi-stable-switches-govern-the-cell-fate-commitment-of-embryonic-stem-cells
#23
JOURNAL ARTICLE
Amitava Giri, Sandip Kar
The development of embryonic stem (ES) cells to extraembryonic trophectoderm and primitive endoderm lineages manifests distinct steady-state expression patterns of two key transcription factors-Oct4 and Nanog. How dynamically such kind of steady-state expressions are maintained remains elusive. Herein, we demonstrate that steady-state dynamics involving two bistable switches which are interlinked via a stepwise (Oct4) and a mushroom-like (Nanog) manner orchestrate the fate specification of ES cells. Our hypothesis qualitatively reconciles various experimental observations and elucidates how different feedback and feedforward motifs orchestrate the extraembryonic development and stemness maintenance of ES cells...
February 26, 2024: FEBS Letters
https://read.qxmd.com/read/38405756/scalable-and-efficient-generation-of-mouse-primordial-germ-cell-like-cells
#24
Xinbao Ding, Liangdao Li, Jingyi Gao, Dain Yi, John C Schimenti
Primordial germ cells (PGCs) are the founder cells of the germline. The ability to generate PGC-like cells (PGCLCs) from pluripotent stem cells has advanced our knowledge of gametogenesis and holds promise for developing infertility treatments. However, generating an ample supply of PGCLCs for demanding applications such as high-throughput genetic screens has been a limitation. Here, we demonstrated that simultaneous overexpressing 4 transcriptional factors - Nanog and three PGC master regulators Prdm1 , Prdm14 and Tfap2c - in suspended mouse epiblast like cells (EpiLCs) and formative embryonic stem cells (ESCs) results in efficient and cost-effective production of PGCLCs...
February 15, 2024: bioRxiv
https://read.qxmd.com/read/38400679/are-embryonic-stem-cell-markers-and-aldh1a1-relevant-in-the-context-of-breast-cancer-estrogen-positivity
#25
JOURNAL ARTICLE
Noha A Mousa, Amal Hussein, Noha M Elemam, Ghada Mohammed, Mona Elwany, Tasneem Basha, Amal A AlHammadi, Rana S Majzob, Iman M Talaat
BACKGROUND: Embryonic pluripotency markers are recognized for their role in ER- BC aggressiveness, but their significance in ER+ BC remains unclear. This study aims to investigate the prevalence of expression of pluripotency markers in ER+ BC and their effect on survival and prognostic indicators. METHODS: We analyzed data of ER+ BC patients from three large cancer datasets to assess the expression of three pluripotency markers (NANOG, SOX-2, and OCT4), and the stem cell marker ALDH1A1...
February 2024: Cancer Medicine
https://read.qxmd.com/read/38397173/the-impact-of-psilocybin-on-high-glucose-lipid-induced-changes-in-ins-1-cell-viability-and-dedifferentiation
#26
JOURNAL ARTICLE
Esmaeel Ghasemi Gojani, Bo Wang, Dong-Ping Li, Olga Kovalchuk, Igor Kovalchuk
Serotonin emerges as a pivotal factor influencing the growth and functionality of β-cells. Psilocybin, a natural compound derived from mushrooms of the Psilocybe genus, exerts agonistic effects on the serotonin 5-HT2A and 5-HT2B receptors, thereby mimicking serotonin's behavior. This study investigates the potential impacts of psilocybin on β-cell viability, dedifferentiation, and function using an in vitro system. The INS-1 832/13 Rat Insulinoma cell line underwent psilocybin pretreatment, followed by exposure to high glucose-high lipid (HG-HL) conditions for specific time periods...
January 29, 2024: Genes
https://read.qxmd.com/read/38396088/3d-culture-of-alginate-hyaluronic-acid-hydrogel-supports-the-stemness-of-human-mesenchymal-stem-cells
#27
JOURNAL ARTICLE
Amorn Pangjantuk, Palakorn Kaokaen, Phongsakorn Kunhorm, Nipha Chaicharoenaudomrung, Parinya Noisa
The three-dimensional (3D) cell culture system is being employed more frequently to investigate cell engineering and tissue repair due to its close mimicry of in vivo microenvironments. In this study, we developed natural biomaterials, including hyaluronic acid, alginate, and gelatin, to mimic the creation of a 3D human mesenchymal stem cell (hMSC) extracellular environment and selected hydrogels with high proliferation capacity for 3D MSC culture. Human mesenchymal stem cells were encapsulated within hydrogels, and an investigation was conducted into the effects on cell viability and proliferation, stemness properties, and telomere activity compared to the 2D monolayer culture...
February 23, 2024: Scientific Reports
https://read.qxmd.com/read/38395976/complex-regulatory-networks-influence-pluripotent-cell-state-transitions-in-human-ipscs
#28
JOURNAL ARTICLE
Timothy D Arthur, Jennifer P Nguyen, Agnieszka D'Antonio-Chronowska, Hiroko Matsui, Nayara S Silva, Isaac N Joshua, André D Luchessi, William W Young Greenwald, Matteo D'Antonio, Martin F Pera, Kelly A Frazer
Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized...
February 23, 2024: Nature Communications
https://read.qxmd.com/read/38394865/apigenin-enhances-sorafenib-anti-tumour-efficacy-in-hepatocellular-carcinoma
#29
JOURNAL ARTICLE
Deepti Singh, Mohammad Afsar Khan, Dhruv Mishra, Aditya Goel, Mairaj Ahmed Ansari, Kafil Akhtar, Hifzur R Siddique
BACKGROUND: The "one drug-one target" paradigm has various limitations affecting drug efficacy, such as resistance profiles and adverse effects. Combinational therapies help reduce unexpected off-target effects and accelerate therapeutic efficacy. Sorafenib- an FDA-approved drug for liver cancer, has multiple limitations. Therefore, it is recommended to identify an agent that increases its effectiveness and reduces toxicity. In this regard, Apigenin, a plant flavone, would be an excellent option to explore...
February 22, 2024: Translational Oncology
https://read.qxmd.com/read/38385086/poz-btb-and-at-hook-containing-zinc-finger-1-patz1-suppresses-differentiation-and-regulates-metabolism-in-human-embryonic-stem-cells
#30
JOURNAL ARTICLE
Min Huang, Xiaohua Liao, Xuepeng Wang, Yiwei Qian, Wensheng Zhang, Guokai Chen, Qiang Wu
Human embryonic stem cells (hESCs) can proliferate infinitely (self-renewal) and give rise to almost all types of somatic cells (pluripotency). Hence, understanding the molecular mechanism of pluripotency regulation is important for applications of hESCs in regenerative medicine. Here we report that PATZ1 is a key factor that regulates pluripotency and metabolism in hESCs. We found that depletion of PATZ1 is associated with rapid downregulation of master pluripotency genes and prominent deceleration of cell growth...
2024: International Journal of Biological Sciences
https://read.qxmd.com/read/38382833/generation-of-3d-melanoma-models-using-an-assembloid-based-approach
#31
JOURNAL ARTICLE
Daniel B Rodrigues, Helena R Moreira, Mariana Jarnalo, Ricardo Horta, Alexandra P Marques, Rui L Reis, Rogério P Pirraco
While 3D tumor models have greatly evolved over the past years, there is still a strong requirement for more biosimilar models which are capable of recapitulating cellular crosstalk within the tumor microenvironment while equally displaying representative levels of tumor aggressiveness and invasion. Herein, we disclose an assembloid melanoma model based on the fusion of individual stromal multicellular spheroids (MCSs). In contrast to more traditional tumor models, we show that it is possible to develop self-organizing, heterotypic melanoma models where tumor cells present stem-cell like features like up-regulated pluripotency master regulators SOX2, POU5F1 and NANOG...
February 19, 2024: Acta Biomaterialia
https://read.qxmd.com/read/38374654/colibactin-producing-escherichia-coli-enhance-resistance-to-chemotherapeutic-drugs-by-promoting-epithelial-to-mesenchymal-transition-and-cancer-stem-cell-emergence
#32
JOURNAL ARTICLE
Guillaume Dalmasso, Antony Cougnoux, Tiphanie Faïs, Virginie Bonnin, Benoit Mottet-Auselo, Hang Tt Nguyen, Pierre Sauvanet, Nicolas Barnich, Marine Jary, Denis Pezet, Julien Delmas, Richard Bonnet
Human colorectal cancers (CRCs) are readily colonized by colibactin-producing E. coli (CoPEC). CoPEC induces DNA double-strand breaks, DNA mutations, genomic instability, and cellular senescence. Infected cells produce a senescence-associated secretory phenotype (SASP), which is involved in the increase in tumorigenesis observed in CRC mouse models infected with CoPEC. This study investigated whether CoPEC, and the SASP derived from CoPEC-infected cells, impacted chemotherapeutic resistance. Human intestinal epithelial cells were infected with the CoPEC clinical 11G5 strain or with its isogenic mutant, which is unable to produce colibactin...
2024: Gut Microbes
https://read.qxmd.com/read/38374014/curcumin-enhances-the-anti-cancer-efficacy-of-cdk4-6-inhibitors-in-prostate-cancer
#33
JOURNAL ARTICLE
Huandong Zhao, Ruimin Ding, Jiarui Han
OBJECTIVE: This study aimed to investigate the potential of combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with curcumin (Cur), a natural compound known for its anti-aging properties, to enhance the anti-cancer efficacy in prostate cancer (PCa). METHODS: The cell viability was determined by cell counting kit-8 assay, colony forming assay and cell invasion. The cell cycle and mRNA levels of p16 (cyclin dependent kinase inhibitor 2A, CDKN2A), p21 (cyclin dependent kinase inhibitor 1A, CDKN1A) and Rb (RB transcriptional corepressor) were detected by flow cytometry and quantitative real-time polymerase chain reaction, respectively...
January 2024: Archivos Españoles de Urología
https://read.qxmd.com/read/38354648/generation-of-ipsc-lines-derived-from-skin-fibroblasts-of-two-healthy-controls-using-non-transmissible-form-of-sendai-virus
#34
JOURNAL ARTICLE
A Orsi, V Serpieri, C Mazzotta, M Cotta Ramusino, E Rossi, S Cerri, E M Valente
We established two iPSC lines starting from skin fibroblasts of two healthy individuals using Sendai-virus-based technique. The obtained iPSCs were characterized showing same STR profile as starting fibroblasts, normal karyotype, loss of stemness vectors, expression of stemness markers, both through real-time PCR and immunofluorescence, (OCT4, SOX2, TRA-1-60, NANOG and SSEA4) and in vitro differentiation into three germ layers.
February 8, 2024: Stem Cell Research
https://read.qxmd.com/read/38354087/proline-restores-mitochondrial-function-and-reverses-aging-hallmarks-in-senescent-cells
#35
JOURNAL ARTICLE
Debanik Choudhury, Na Rong, Hamsa Vardini Senthil Kumar, Sydney Swedick, Ronel Z Samuel, Pihu Mehrotra, John Toftegaard, Nika Rajabian, Ramkumar Thiyagarajan, Ashis K Podder, Yulun Wu, Shahryar Shahini, Kenneth L Seldeen, Bruce Troen, Pedro Lei, Stelios T Andreadis
Mitochondrial dysfunction is a hallmark of cellular senescence, with the loss of mitochondrial function identified as a potential causal factor contributing to senescence-associated decline in cellular functions. Our recent findings revealed that ectopic expression of the pluripotency transcription factor NANOG rejuvenates dysfunctional mitochondria of senescent cells by rewiring metabolic pathways. In this study, we report that NANOG restores the expression of key enzymes, PYCR1 and PYCR2, in the proline biosynthesis pathway...
February 27, 2024: Cell Reports
https://read.qxmd.com/read/38350724/decoupling-the-influence-of-poly-3-4-ethylenedioxythiophene-collagen-composite-characteristics-on-cell-stemness
#36
JOURNAL ARTICLE
Rebecca L Keate, Joshua Tropp, Ruiheng Wu, Anthony J Petty, Guillermo A Ameer, Jonathan Rivnay
Conductive polymers (CPs) are widely studied for their ability to influence a myriad of tissue systems. While their mixed ionic/electronic conductivity is commonly considered the primary driver of these benefits, the mechanisms by which CPs influence cell fate remain unclear. In this study, CP-biomaterial interactions are investigated using collagen, due to its widespread prevalence throughout the body and in tissue engineering constructs. Collagen is functionalized with both electrostatically and covalently bound derivatives of the CP poly(3,4-ethylenedioxythiophene) (PEDOT) doped via backbone-tethered sulfonate groups, which enable high solubility and loading to the collagen biomatrix...
February 13, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38349796/targeting-the-glycan-epitope-type-i-n-acetyllactosamine-enables-immunodepletion-of-human-pluripotent-stem-cells-from-early-differentiated-cells
#37
JOURNAL ARTICLE
Charlotte Rossdam, Smilla Brand, Julia Beimdiek, Astrid Oberbeck, Marco Darius Albers, Ortwin Naujok, Falk F R Buettner
Cell surface biomarkers are fundamental for specific characterization of human pluripotent stem cells (hPSCs). Importantly, they can be applied for hPSC enrichment and/or purification but also to remove potentially teratoma-forming hPSCs from differentiated populations before clinical application. Several specific markers for hPSCs are glycoconjugates comprising the glycosphingolipid (GSL)-based glycans SSEA-3 and SSEA-4. We applied an analytical approach based on multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection to quantitatively assess the GSL glycome of human embryonic stem cells and human induced pluripotent stem cells as well as during early stages of differentiation into mesoderm, endoderm, and ectoderm...
February 13, 2024: Glycobiology
https://read.qxmd.com/read/38349260/calcrl-knockdown-suppresses-cancer-stemness-and-chemoresistance-in-acute-myeloid-leukemia-with-flt3-itd-and-dnm3ta-r882-double-mutations
#38
JOURNAL ARTICLE
Shanhao Tang, Huiling Zhu, Lixia Sheng, Qitian Mu, Yi Wang, Kaihong Xu, Miao Zhou, Zhijuan Xu, An Wu, Guifang Ouyang
Acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (FLT3-ITD) and DNA methyltransferase 3A (DNMT3A) R882 double mutations had a worse prognosis compared with AML with FLT3-ITD or DNMT3A R882 single mutation. This study was designed to explore the specific role of Calcitonin Receptor Like (CALCRL) in AML with FLT3-ITD and DNMT3A R882 double mutations. MOLM13 cells were transduced with CRISPR knockout sgRNA constructs to establish the FTL3-ITD and DNMT3A-R882 double-mutated AML cell model...
February 2024: Drug Development Research
https://read.qxmd.com/read/38344977/synthesis-and-biophysical-properties-of-triazole-incorporated-pmos-tzpmos-a-convergent-click-ligation-approach
#39
JOURNAL ARTICLE
Arpan Banerjee, Arnab Das, Atanu Ghosh, Abhishek Gupta, Surajit Sinha
The synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) incorporating single or double triazole rings in the backbone has been achieved via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The synthetic approach implemented is fundamentally convergent, involving the ligation of a 5'-azide PMO fragment to a 3'-alkyne fragment both in solution and on solid support. To access the 3'-alkyne PMO fragment, we synthesized 3'- N -propargyl chlorophosphoramidate morpholino monomers for all four nucleobases...
February 12, 2024: Journal of Organic Chemistry
https://read.qxmd.com/read/38342310/zfp982-confers-mouse-embryonic-stem-cell-characteristics-by-regulating-expression-of-nanog-zfp42-and-dppa3
#40
JOURNAL ARTICLE
Fariba Dehghanian, Patrick Piero Bovio, Fabian Gather, Simone Probst, Amirhosein Naghsh-Nilchi, Tanja Vogel
BACKGROUND: Understanding the genetic underpinnings of protein networks conferring stemness is of broad interest for basic and translational research. METHODS: We used multi-omics analyses to identify and characterize stemness genes, and focused on the zinc finger protein 982 (Zfp982) that regulates stemness through the expression of Nanog, Zfp42, and Dppa3 in mouse embryonic stem cells (mESC). RESULTS: Zfp982 is expressed in stem cells, and binds to chromatin through a GCAGAGKC motif, for example near the stemness genes Nanog, Zfp42, and Dppa3...
February 9, 2024: Biochimica et Biophysica Acta. Molecular Cell Research
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