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mitochondria in stem cells

Kiriko Kaneko, Yoshiko Kubota, Kazumi Nomura, Haruka Hayashimoto, Taisei Chida, Naoto Yoshino, Marina Wayama, Katsutoshi Ogasawara, Yukio Nakamura, Ikuo Tooyama, Kazumichi Furuyama
ALAS2 gene mutations cause X-linked sideroblastic anemia. The presence of ring sideroblasts in a patient's bone marrow is the hallmark of sideroblastic anemia, but the precise mechanisms underlying sideroblast formation are largely unknown. Using a genome editing system, a mutation was introduced in the erythroid-specific enhancer of the ALAS2 gene in HUDEP2 cells, which were derived from human umbilical stem cells and can produce erythrocytes. The established cell line, termed HA2low, expressed less ALAS2 mRNA than did wild-type cells, even after erythroid differentiation...
June 13, 2018: Experimental Hematology
Yu-Ling Ni, Chang-Heng Hsieh, Jing-Ping Wang, Kang Fang
Therapy by targeting cancer stem cells (CSCs) is an eligible method to eradicate malignant human tumors. A synthetic triepoxide derivative, teroxirone, was reported effective against growth of human lung cancer cells by injuring cellular mitochondria functions. And yet it remains unclear if the residual but malicious CSCs can be effectively dissipated as a result of treatment. The current study further affirmed that teroxirone inhibited propagation of CSCs as enriched from NSCLC cells by inducing p53 that lead to ultimate apoptosis...
June 13, 2018: Chemico-biological Interactions
Yang Lv, Bo Liu, Yuan Liu, Haoyu Wang, Haiping Wang
Transforming growth factor β1 (TGF-β1) and salvianolic acid B (Sal-B) are key signaling factors for stem cell differentiation into cardiomyocytes (CMs). The present study compared the biological effect of TGF-β1 and Sal-B, alone or in combination, on bone marrow mesenchymal stromal cells (BMSCs) that differentiate into myocardial-like cells in a simulated myocardial microenvironment in vitro . BMSCs were isolated from bones of limbs of 10 male Sprague Dawley rats and cultured. The 2nd-generation BMSCs were co-incubated with TGF-β1 and Sal-B, alone or in combination, for 72 h...
June 2018: Experimental and Therapeutic Medicine
Xiaoqing Song, Lining Su, Haifeng Yin, Jin Dai, Huiping Wei
As a primary active ingredient of safflor yellow, hydroxysafflor yellow A (HSYA) exhibits notable antioxidative and neuroprotective effects. The aim of the present study was to investigate the protective effects of HSYA in mesenchymal stem cells (MSCs) exposed to hypoxia (5% O2 ) and serum deprivation (H/SD), and to explore the mechanisms underlying HSYA-mediated protection. Under H/SD conditions, HSYA was applied to protect MSCs against injury. Cell viability, proliferation, apoptosis and reactive oxygen species (ROS) levels were determined using an 5-ethynyl-2'-deoxyuridine assay, MTT assay, Hoechst 33342/propidium iodide and 2',7'-dichlorodihydrofluorescein diacetate staining, respectively...
June 2018: Experimental and Therapeutic Medicine
Daniel Little, Christin Luft, Olukunbi Mosaku, Maëlle Lorvellec, Zhi Yao, Sébastien Paillusson, Janos Kriston-Vizi, Sonia Gandhi, Andrey Y Abramov, Robin Ketteler, Michael J Devine, Paul Gissen
Mitochondrial dysfunction is implicated in many neurodegenerative diseases including Parkinson's disease (PD). Induced pluripotent stem cells (iPSCs) provide a unique cell model for studying neurological diseases. We have established a high-content assay that can simultaneously measure mitochondrial function, morphology and cell viability in iPSC-derived dopaminergic neurons. iPSCs from PD patients with mutations in SNCA and unaffected controls were differentiated into dopaminergic neurons, seeded in 384-well plates and stained with the mitochondrial membrane potential dependent dye TMRM, alongside Hoechst-33342 and Calcein-AM...
June 13, 2018: Scientific Reports
Yu-Ting Wu, Kun-Ting Chi, Yueh-Wen Lan, Jui-Chi Chan, Yi-Shing Ma, Yau-Huei Wei
Upregulation of mitochondrial function and oxidative metabolism is a hallmark in the differentiation of stem cells. However, the mechanism underlying the metabolic reprogramming and upregulation of mitochondrial function during the differentiation of human mesenchymal stem cells (hMSCs) is largely unclear. Sirt3 has emerged as a sensor in regulating mitochondrial function and antioxidant defense system in cellular response to energy demand or environmental stimuli, but its roles in stem cell differentiation has not been fully understood...
June 14, 2018: Free Radical Research
Marthe H R Ludtmann, Plamena R Angelova, Mathew H Horrocks, Minee L Choi, Margarida Rodrigues, Artyom Y Baev, Alexey V Berezhnov, Zhi Yao, Daniel Little, Blerida Banushi, Afnan Saleh Al-Menhali, Rohan T Ranasinghe, Daniel R Whiten, Ratsuda Yapom, Karamjit Singh Dolt, Michael J Devine, Paul Gissen, Tilo Kunath, Morana Jaganjac, Evgeny V Pavlov, David Klenerman, Andrey Y Abramov, Sonia Gandhi
Protein aggregation causes α-synuclein to switch from its physiological role to a pathological toxic gain of function. Under physiological conditions, monomeric α-synuclein improves ATP synthase efficiency. Here, we report that aggregation of monomers generates beta sheet-rich oligomers that localise to the mitochondria in close proximity to several mitochondrial proteins including ATP synthase. Oligomeric α-synuclein impairs complex I-dependent respiration. Oligomers induce selective oxidation of the ATP synthase beta subunit and mitochondrial lipid peroxidation...
June 12, 2018: Nature Communications
Xiang Zhou
5-Formyluracil (5fU), which known as a vital natural nucleobase, is widely present in organisms. Despite the blooming development of sensor designs for organic fluorescent molecules for selective targeting applications, biocompatible and easily operated probe designs that are based on natural nucleobase modifications have been rarely reported. In this paper, we introduce the idea of 5fU as a multifunctional building block to facilitate the design and synthetic development of biosensors. The azide group was derived from the sugar of a nucleoside, which can be further used in selective binding cells or organelles through click chemistry with alkynyl-modified targeting groups...
June 12, 2018: Angewandte Chemie
Yasuhiro Watanabe, Takashi Matsuba, Mami Nakanishi, Mio Une, Ritsuko Hanajima, Kenji Nakashima
BACKGROUND: Tetanus neurotoxin (TeNT) is taken up at nerve terminals and undergoes retrograde migration. The toxic properties of TeNT reside in the toxin light chain (L), but like complete TeNT, the TeNT heavy chain (TTH) and the C-terminal domain (TTC) alone can bind and enter into neurons. Here, we explored whether atoxic fragments of TeNT could act as drug delivery vehicles in neurons. In this study, we used Bcl-2, a protein known to have anti-apoptotic properties in vivo and in vitro, as a parcel to couple to TeNT fragments...
June 11, 2018: BMC Biotechnology
Jorge S Valadas, Giovanni Esposito, Dirk Vandekerkhove, Katarzyna Miskiewicz, Liesbeth Deaulmerie, Susanna Raitano, Philip Seibler, Christine Klein, Patrik Verstreken
Parkinson's disease patients report disturbed sleep patterns long before motor dysfunction. Here, in parkin and pink1 models, we identify circadian rhythm and sleep pattern defects and map these to specific neuropeptidergic neurons in fly models and in hypothalamic neurons differentiated from patient induced pluripotent stem cells (iPSCs). Parkin and Pink1 control the clearance of mitochondria by protein ubiquitination. Although we do not observe major defects in mitochondria of mutant neuropeptidergic neurons, we do find an excess of endoplasmic reticulum-mitochondrial contacts...
June 1, 2018: Neuron
Elisabet Cuyàs, Sara Verdura, Núria Folguera-Blasco, Cristian Bastidas-Velez, Ángel G Martin, Tomás Alarcón, Javier A Menendez
Unraveling the key mechanisms governing the retention versus loss of the cancer stem cell (CSC) state would open new therapeutic avenues to eradicate cancer. Mitochondria are increasingly recognized key drivers in the origin and development of CSC functional traits. We here propose the new term "mitostemness" to designate the mitochondria-dependent signaling functions that, evolutionary rooted in the bacterial origin of mitochondria, regulate the maintenance of CSC self-renewal and resistance to differentiation...
June 9, 2018: Cell Cycle
Ying-Chu Chen, Yu-Hsiang Yu
Brown adipocyte lineage commitment and differentiation are under complex regulation. Brown adipocytes are derived from mesenchymal stem cells (MSCs). Whether porcine bone marrow-derived MSCs (BM-MSCs) possess the potential to differentiate into brown adipocytes remains unclear. In the current study, we evaluated the ability of porcine BM-MSCs to differentiate into brown adipocytes and browning of differentiated adipocytes. We found that similar to rodent models, bone morphogenetic protein 7 (BMP7) was able to trigger the commitment of BM-MSCs to the brown adipocyte lineage by elevating expression of marker genes, nrf-1, tfam, zic1 and pgc-1α (P < 0...
June 7, 2018: Journal of Animal Science
David C Schöndorf, Dina Ivanyuk, Pascale Baden, Alvaro Sanchez-Martinez, Silvia De Cicco, Cong Yu, Ivana Giunta, Lukas K Schwarz, Gabriele Di Napoli, Vasiliki Panagiotakopoulou, Sigrun Nestel, Marcus Keatinge, Jan Pruszak, Oliver Bandmann, Bernd Heimrich, Thomas Gasser, Alexander J Whitworth, Michela Deleidi
While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease...
June 5, 2018: Cell Reports
Rajendrarao Sumitha, Venkataswamy M Manjunatha, Rajesh K Sabitha, Phalguni A Alladi, A Nalini, Laxmi T Rao, B K Chandrasekhar Sagar, Harry W M Steinbusch, Boris W Kramer, T N Sathyaprabha, Trichur R Raju
Disease modeling has become challenging in the context of amyotrophic lateral sclerosis (ALS), as obtaining viable spinal motor neurons from postmortem patient tissue is an unlikely possibility. Limitations in the animal models due to their phylogenetic distance from human species hamper the success of translating possible findings into therapeutic options. Accordingly, there is a need for developing humanized models as a lead towards identifying successful therapeutic possibilities. In this study, human embryonic stem cells-BJNHem20-were differentiated into motor neurons expressing HB9, Islet1, and choline acetyl transferase using retinoic acid and purmorphamine...
June 1, 2018: Molecular Neurobiology
Kyoko Ito, Keisuke Ito
Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process...
May 25, 2018: Experimental Hematology
Rhys Pritchard, Sara Rodríguez-Enríquez, Silvia Cecelia Pacheco-Velázquez, Vuk Bortnik, Rafael Moreno-Sánchez, Stephen Ralph
Capecitabine induced toxicities such as hand-foot syndrome (HFS) and progression of metastatic cancer are both treatable with concurrent celecoxib as shown in the ADAPT (Activating Cancer Stem Cells from Dormancy And Potentiate for Targeting) trial. In the present study, five commonly used NSAIDs, including celecoxib were compared for their pro-oxidative capacities as cytotoxic drugs against human and mouse metastatic melanoma or breast cancer cells in vitro and the source of cellular ROS production induced by celecoxib was examined in greater detail...
May 22, 2018: Biochemical Pharmacology
James Moon, Hye Ran Kim, Myung Geun Shin
Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system...
September 2018: Annals of Laboratory Medicine
Swatishree Sradhanjali, Mamatha M Reddy
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate dehydrogenase kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it...
May 22, 2018: Current Topics in Medicinal Chemistry
Mayara Pereira Gonçalves, Maria Olívia Mercadante-Simões, Leonardo Monteiro Ribeiro
Latex is a complex plant secretion with both ecological and economic importance. There is little information currently available on the cytological aspects of the ontogenesis of anastomosed laticifers, the ducts originating through the lysis of adjacent cell walls. Hancornia speciosa is a tree typical of the Cerrado (neotropical savanna) biome. Its latex has medicinal value and is also used to produce rubber. The ontogenesis of its laticifers and the process of latex synthesis are described here. Structural, cytochemical, and ultrastructural analyses of the stem apex and phytochemical analyses of the latex were performed...
May 18, 2018: Protoplasma
Yuting He, Xueqi Gan, Ling Zhang, Beilei Liu, Zhuoli Zhu, Tao Li, Junfei Zhu, Junsheng Chen, Haiyang Yu
Oxygen deficiency is associated with various oral diseases, including chronic periodontitis, age-related alveolar bone loss and mechanical stress-linked cell injury from orthodontic appliances. Nevertheless, our understanding of the impact of hypoxia on periodontal tissues and its biochemical mechanism is still rudimentary. The purpose of this research was to elucidate the effects of hypoxia on the apoptosis of human periodontal ligament stem cells (PDLSCs) in vitro and the underlying mechanism. Herein, we showed that CoCl2 triggered cell dysfunction in human PDLSCs in a concentration-dependent manner and resulted in cell apoptosis and oxidative stress overproduction and accumulation in PDLSCs...
May 16, 2018: American Journal of Physiology. Cell Physiology
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