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https://www.readbyqxmd.com/read/29764980/interplay-of-cell-cell-contacts-and-rhoa-mrtf-a-signaling-regulates-cardiomyocyte-identity
#1
Tatjana Dorn, Jessica Kornherr, Elvira I Parrotta, Dorota Zawada, Harold Ayetey, Gianluca Santamaria, Laura Iop, Elisa Mastantuono, Daniel Sinnecker, Alexander Goedel, Ralf J Dirschinger, Ilaria My, Svenja Laue, Tarik Bozoglu, Christian Baarlink, Tilman Ziegler, Elisabeth Graf, Rabea Hinkel, Giovanni Cuda, Stefan Kääb, Andrew A Grace, Robert Grosse, Christian Kupatt, Thomas Meitinger, Austin G Smith, Karl-Ludwig Laugwitz, Alessandra Moretti
Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29751772/expression-profiling-of-cell-intrinsic-regulators-in-the-process-of-differentiation-of-human-ipscs-into-retinal-lineages
#2
Jen-Hua Chuang, Aliaksandr A Yarmishyn, De-Kuang Hwang, Chih-Chien Hsu, Mong-Lien Wang, Yi-Ping Yang, Ke-Hung Chien, Shih-Hwa Chiou, Chi-Hsien Peng, Shih-Jen Chen
BACKGROUND: Differentiation of human induced pluripotent stem cells (hiPSCs) into retinal lineages offers great potential for medical application. Therefore, it is of crucial importance to know the key intrinsic regulators of differentiation and the specific biomarker signatures of cell lineages. METHODS: In this study, we used microarrays to analyze transcriptomes of terminally differentiated retinal ganglion cell (RGC) and retinal pigment epithelium (RPE) lineages, as well as intermediate retinal progenitor cells of optic vesicles (OVs) derived from hiPSCs...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29729503/direct-conversion-of-human-pluripotent-stem-cells-into-cranial-motor-neurons-using-a-piggybac-vector
#3
Riccardo De Santis, Maria Giovanna Garone, Francesca Pagani, Valeria de Turris, Silvia Di Angelantonio, Alessandro Rosa
Human pluripotent stem cells (PSCs) are widely used for in vitro disease modeling. One of the challenges in the field is represented by the ability of converting human PSCs into specific disease-relevant cell types. The nervous system is composed of a wide variety of neuronal types with selective vulnerability in neurodegenerative diseases. This is particularly relevant for motor neuron diseases, in which different motor neurons populations show a different susceptibility to degeneration. Here we developed a fast and efficient method to convert human induced Pluripotent Stem Cells into cranial motor neurons of the branchiomotor and visceral motor subtype...
April 27, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29700121/genetic-lineage-tracing-of-non-myocyte-population-by-dual-recombinases
#4
Yan Li, Lingjuan He, Xiuzhen Huang, Shirin Issa Bhaloo, Huan Zhao, Shaohua Zhang, Wenjuan Pu, Xueying Tian, Yi Li, Qiaozhen Liu, Wei Yu, Libo Zhang, Xiuxiu Liu, Kuo Liu, Juan Tang, Hui Zhang, Dongqing Cai, Ralf H Adams, Qingbo Xu, Kathy O Lui, Bin Zhou
Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1+ , Bmi1+ , Isl1+ or Abcg2+ CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart...
April 26, 2018: Circulation
https://www.readbyqxmd.com/read/29678908/the-lim-homeodomain-protein-isl1-mediates-the-function-of-tcf7l2-in-pancreatic-beta-cells
#5
Weijuan Shao, Vivian Szeto, Zhuolun Song, Lili Tian, Zhong-Ping Feng, Cristina M Nostro, Tianru Jin
Pancreatic β-cell Tcf7l2 deletion or its functional knockdown suggested the essential role of this Wnt pathway effector in controlling insulin secretion, glucose homeostasis, and β-cell gene expression. As the LIM homeodomain protein Isl1 is a suggested Wnt pathway downstream target, we hypothesize that it mediates metabolic functions of Tcf7l2. We aimed to determine the role of Isl1 in mediating the function of Tcf7l2 and the incretin hormone GLP-1 in pancreatic β-cells. Effect of dominant negative TCF7L2 (TCF7L2DN) mediated Wnt pathway functional knockdown on Isl1 expression was determined in βTCFDN mouse islets and in the rat insulinoma cell line INS-1 832/13...
April 20, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29666277/disparate-binding-kinetics-by-an-intrinsically-disordered-domain-enables-temporal-regulation-of-transcriptional-complex-formation
#6
Neil O Robertson, Ngaio C Smith, Athina Manakas, Mahiar Mahjoub, Gordon McDonald, Ann H Kwan, Jacqueline M Matthews
Intrinsically disordered regions are highly represented among mammalian transcription factors, where they often contribute to the formation of multiprotein complexes that regulate gene expression. An example of this occurs with LIM-homeodomain (LIM-HD) proteins in the developing spinal cord. The LIM-HD protein LHX3 and the LIM-HD cofactor LDB1 form a binary complex that gives rise to interneurons, whereas in adjacent cell populations, LHX3 and LDB1 form a rearranged ternary complex with the LIM-HD protein ISL1, resulting in motor neurons...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29653101/%C3%AE-1-integrin-is-a-cell-autonomous-factor-mediating-the-numb-pathway-for-cardiac-progenitor-maintenance
#7
Brian Gibbs, Lincoln Shenje, Peter Andersen, Matthew Miyamoto, Chulan Kwon
Proper control of multipotent/stem cell number and fate is essential for ensuing organ formation during development. β1-integrin, a subfamily of cell surface receptors, has a conserved role in maintenance of multipotent/stem cells, including renal progenitor cells, follicle stem cells, epidermal stem cells and neural stem cells. However, it remains unclear whether β1-integrin has a role in cardiac progenitor cell (CPC) development. Here we show that a mesodermal deletion of β1-integrin decreases Isl1+ cell number in the second pharyngeal arch (PA2), where CPCs undergo renewal and expansion...
April 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29619236/evaluation-of-the-isl1-gene-in-the-pathogenesis-of-bladder-exstrophy-in-a-swedish-cohort
#8
Samara Arkani, Jia Cao, Johanna Lundin, Daniel Nilsson, Thomas Källman, Gillian Barker, Gundela Holmdahl, Christina Clementsson Kockum, Hans Matsson, Agneta Nordenskjöld
Bladder exstrophy is a congenital closure defect of the urinary bladder with a profound effect on morbidity. Although the malformation is usually sporadic, a genetic background is supported by an increased recurrence risk in relatives, higher concordance rates in monozygotic twins and several associated chromosomal aberrations. Recently, the ISL1 gene was presented as a candidate gene for bladder exstrophy and epispadias complex (BEEC) development in two different studies. In our study, we screened for genetic variants in the ISL1 gene in DNA from 125 Swedish patients using Sanger sequencing and array-CGH analysis...
2018: Human Genome Variation
https://www.readbyqxmd.com/read/29606507/human-isl1-ventricular-progenitors-self-assemble-into-an-in-vivo-functional-heart-patch-and-preserve-cardiac-function-post-infarction
#9
Kylie S Foo, Miia L Lehtinen, Chuen Yan Leung, Xiaojun Lian, Jiejia Xu, Wendy Keung, Lin Geng, Terje R S Kolstad, Sebastian Thams, Andy On-Tik Wong, Nicodemus Wong, Kristine Bylund, Chikai Zhou, Xiaobing He, Shao-Bo Jin, Jonathan Clarke, Urban Lendahl, Ronald A Li, William E Louch, Kenneth R Chien
The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo...
February 17, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29568936/islet-1-promotes-the-proliferation-and-invasion-and-inhibits-the-apoptosis-of-a375-human-melanoma-cells
#10
Xiaoling Zhu, Yuzhen Li, Qinggang Meng
The aim of this study was to examine the effects of the insulin gene enhancer-binding protein, islet-1 (ISL1), on the proliferation, invasion and apoptosis of the human melanoma cell line, A375. An ISL1 overexpression lentiviral vector was constructed and transfected into the A375 cells. The proliferation of the A375 cells transfected with the ISL1 vector (termed A375/ISL1 cells) was examined by MTT assay, flow cytometry and TUNEL assay, and cell invasion was examined by Transwell assay. The expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were measured by qPCR and western blot analysis; the expression levels of Akt and p-Akt were measured in the cells treated with vascular endothelial growth factor (VEGF) and the PI3K/Akt inhibitor, LY294002, by western blot analysis...
March 14, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29531855/short-term-hypoxia-improves-early-cardiac-progenitor-cell-function-in-vitro
#11
Ivan Hernandez, Jonathan M Baio, Eric Tsay, Aida F Martinez, Tania I Fuentes, Leonard L Bailey, Nahidh W Hasaniya, Mary Kearns-Jonker
The use of cardiovascular progenitor cells (CPCs) to repair damaged myocardium has been the focus of intense research. Previous reports have shown that pretreatments, including hypoxia, improve cell function. However, the age-dependent effects of short-term hypoxia on CPCs, and the role of signaling in these effects, are unknown. Cloned neonatal and adult CPCs expressing Isl1, c-Kit, KDR, PDGFRA, and CXCR4, were preconditioned using hypoxia (1% O2 for six hours). Intracellular signaling pathway changes were modeled using Ingenuity Pathway Analysis (IPA), while qRT-PCR, flow cytometry, and immunoblotting were used to measure pathway activation...
2018: American Journal of Stem Cells
https://www.readbyqxmd.com/read/29512771/screening-pathogenic-genes-in-oral-squamous-cell-carcinoma-based-on-the-mrna-expression-microarray-data
#12
Yang Ding, Pengfei Liu, Shengsheng Zhang, Lin Tao, Jianmin Han
Oral squamous cell carcinoma (OSCC) is one of the most common malignancies and its survival rate has barely improved over the past few decades. The purpose of this study was to screen pathogenic genes of OSCC via microarray analysis. The mRNA expression microarray datasets (GSE2280 and GSE3524) were downloaded from the Gene Expression Omnibus (GEO) database. In GSE2280, there were 22 OSCC samples without metastasis and 5 OSCC samples with lymph node metastasis. In GSE3524, there were 16 OSCC samples and 4 normal tissue samples...
June 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29511614/the-combined-effect-of-pdx1-overexpression-and-shh-manipulation-on-the-function-of-insulin-producing-cells-derived-from-adipose-tissue-stem-cells
#13
Mahmoud Hashemi Tabar, Mohammad Reza Tabandeh, Eskandar Moghimipour, Dian Dayer, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
Pancreatic and duodenal homeobox 1 (Pdx1) and Sonic hedgehog (Shh) are the key regulators of beta-cell function. In vitro experiments have shown that there is significant cooperation between Pdx1 and Shh with regard to the production and maintenance of insulin-producing cells (IPCs). In this study, the combined effect of Pdx1 overexpression and Shh manipulation on the function of adipose tissue-derived IPCs was determined. A eukaryotic expression vector ( Pdx1- pCDNA3.1(+)) was constructed and transfected into a Chinese hamster ovary (CHO) cell line...
March 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29503094/prospective-isolation-of-isl1-cardiac-progenitors-from-human-escs-for-myocardial-infarction-therapy
#14
Zaniar Ghazizadeh, Faranak Fattahi, Mehdi Mirzaei, Delger Bayersaikhan, Jaesuk Lee, Sehyun Chae, Daehee Hwang, Kyunghee Byun, Mehdi Sharifi Tabar, Sara Taleahmad, Shahab Mirshahvaladi, Parisa Shabani, Hananeh Fonoudi, Paul A Haynes, Hossein Baharvand, Nasser Aghdami, Todd Evans, Bonghee Lee, Ghasem Hosseini Salekdeh
The LIM-homeodomain transcription factor ISL1 marks multipotent cardiac progenitors that give rise to cardiac muscle, endothelium, and smooth muscle cells. ISL1+ progenitors can be derived from human pluripotent stem cells, but the inability to efficiently isolate pure populations has limited their characterization. Using a genetic selection strategy, we were able to highly enrich ISL1+ cells derived from human embryonic stem cells. Comparative quantitative proteomic analysis of enriched ISL1+ cells identified ALCAM (CD166) as a surface marker that enabled the isolation of ISL1+ progenitor cells...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29497310/isl1-is-upregulated-in-breast-cancer-and-promotes-cell-proliferation-invasion-and-angiogenesis
#15
Lin Li, Fuwen Sun, Xiaoyan Chen, Minghui Zhang
ISL1 plays a key role in several cancers, including pheochromocytoma, gastrointestinal, pancreatic, and lung tumors and bile duct carcinoma. In order to elucidate the role of ISL1 in breast cancer, we performed quantitative real-time polymerase chain reaction and Western blotting analysis, and we found that ISL1 was upregulated in breast cancer cells and tissues. Moreover, high expression of ISL1 was correlated with tumor size, metastasis, and poor prognosis. Colony formation analysis and CCK-8 analysis revealed that ISL1 facilitated breast cancer cell proliferation...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29485473/cardiac-progenitors-induced-from-human-induced-pluripotent-stem-cells-with-cardiogenic-small-molecule-effectively-regenerate-infarcted-hearts-and-attenuate-fibrosis
#16
Wanling Xuan, Yan Wang, Yaoliang Tang, Ailia Ali, Hong Hu, Mark Maienschein-Cline, Muhammad Ashraf
Cardiac progenitor cells (CPCs) being multipotent offer a promising source for cardiac repair due to their ability to proliferate and multiply into cardiac lineage cells. Here, we explored a novel strategy for human CPCs generation from human induced pluripotent stem cells (hiPSCs) using a cardiogenic small molecule, isoxazole (ISX-9) and their ability to grow in the scar tissue for functional improvement in the infarcted myocardium. CPCs were induced from hiPSCs with ISX-9. CPCs were characterized by immunocytochemistry and RT-PCR...
February 26, 2018: Shock
https://www.readbyqxmd.com/read/29482621/isl1-overexpression-enhances-the-survival-of-transplanted-human-mesenchymal-stem-cells-in-a-murine-myocardial-infarction-model
#17
Qiuling Xiang, Yan Liao, Hua Chao, Weijun Huang, Jia Liu, Haixuan Chen, Dongxi Hong, Zhengwei Zou, Andy Peng Xiang, Weiqiang Li
BACKGROUND: The LIM-homeobox transcription factor islet-1 (ISL1) has been proposed as a marker for cardiovascular progenitor cells. This study investigated whether forced expression of ISL1 in human mesenchymal stem cells (hMSCs) improves myocardial infarction (MI) treatment outcomes. METHODS: The lentiviral vector containing the human elongation factor 1α promoter, which drives the expression of ISL1 (EF1α-ISL1), was constructed using the Multisite Gateway System and used to transduce hMSCs...
February 26, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29480946/lim-homeobox-transcription-factor-isl1-is-required-for-melatonin-synthesis-in-the-pig-pineal-gland
#18
Jinglin Zhang, Jingtao Qiu, Yewen Zhou, Yue Wang, Hongjiao Li, Taojie Zhang, Ying Jiang, Kemian Gou, Sheng Cui
Melatonin is a key hormone that regulates circadian rhythms, metabolism, and reproduction. However, the mechanisms of melatonin synthesis and secretion have not been fully defined. The purpose of this study was to investigate the functions of the LIM homeobox transcription factor Isl1 in regulating melatonin synthesis and secretion in porcine pineal gland. We found that Isl1 is highly expressed in the melatonin-producing cells in the porcine pineal gland. Further functional studies demonstrate that Isl1 knockdown in cultured primary porcine pinealocytes results in the decline of melatonin and arylalkylamine N-acetyltransferase (AANAT) mRNA levels by 29...
February 26, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29445148/temporal-requirements-for-isl1-in-sympathetic-neuron-proliferation-differentiation-and-diversification
#19
Qingquan Zhang, Ru Huang, Youqiong Ye, Xiaoxia Guo, Jun Lu, Fugui Zhu, Xiaohui Gong, Qitong Zhang, Jie Yan, Lina Luo, Shaowei Zhuang, Yihan Chen, Xiaodong Zhao, Sylvia M Evans, Cizhong Jiang, Xingqun Liang, Yunfu Sun
Malformations of the sympathetic nervous system have been associated with cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A better understanding of the factors regulating sympathetic nervous system development is critical to the development of potential therapies. Here, we have uncovered a temporal requirement for the LIM homeodomain transcription factor ISL1 during sympathetic nervous system development by the analysis of two mutant mouse lines: an Isl1 hypomorphic line and mice with Isl1 ablated in neural crest lineages...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29412738/reciprocity-of-action-of-increasing-oct4-and-repressing-p53-in-transdifferentiation-of-mouse-embryonic-fibroblasts-into-cardiac-myocytes
#20
Hongran Wang, Shuying Zhao, Michelle Barton, Todd Rosengart, Austin J Cooney
p53 is a barrier to somatic cell reprogramming. Deletion or transient suppression of p53 increases the efficiency of reprogramming of somatic cells into induced pluripotent stem cells. Whether p53 represents an obstacle to a similar process transdifferentiation of somatic cells is unknown. However, it is predicted that inhibition of p53 would promote transdifferentiation of fibroblasts into cardiomyocytes. In this study, the effect of p53 on the capacity of cardiogenic transdifferentiation is evaluated using p53 wild-type (p53+/+ ), p53 heterozygous mutant (p53+/- ), and p53 homozygous mutant (p53-/- ) mouse embryonic fibroblasts (MEFs)...
February 2018: Cellular Reprogramming
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