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Transdifferentiation

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https://www.readbyqxmd.com/read/28107194/transdifferentiation-of-human-male-germline-stem-cells-to-hepatocytes-in-vivo-via-the-transplantation-under-renal-capsules
#1
Zheng Chen, Minghui Niu, Min Sun, Qingqing Yuan, Chencheng Yao, Jingmei Hou, Hong Wang, Liping Wen, Hongyong Fu, Fan Zhou, Zheng Li, Zuping He
Here we proposed a new concept that human spermatogonial stem cells (SSCs) can transdifferentiate into hepatocytes in vivo. We first established liver injury model of mice by carbon tetrachloride to provide proper environment for human SSC transplantation. Liver mesenchymal cells were isolated from mice and identified phenotypically. Human SSC line was recombined with liver mesenchymal cells, and they were transplanted under renal capsules of nude mice with liver injury. The grafts expressed hepatocyte hallmarks, including ALB, AAT, CK18, and CYP1A2, whereas germ cell and SSC markers VASA and GPR125 were undetected in these cells, implicating that human SSCs were converted to hepatocytes...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28104292/hepatic-prominin-1-expression-is-associated-with-biliary-fibrosis
#2
Marie V Nguyen, Jessica A Zagory, William H Dietz, Alex Park, Michael Fenlon, Menghan Zhao, Jiabo Xu, Ingrid Lua, Nirmala Mavila, Kenji Asahina, Kasper S Wang
BACKGROUND: Intrahepatic biliary fibrosis, as seen with cholestatic liver injuries such as biliary atresia, is mechanistically distinct from fibrosis caused by hepatocyte toxicity. We previously demonstrated the expansion of cells expressing the stem/progenitor cell marker Prominin-1, within regions of developing fibrosis in biliary atresia. Thus, we hypothesized that Prominin-1 expression is biliary fibrosis-specific. METHODS: Gene expression of Prominin-1 was analyzed in adult mice undergoing either cholestatic bile duct ligation or hepatotoxic carbon tetrachloride administration by quantitative polymerase chair reaction...
January 16, 2017: Surgery
https://www.readbyqxmd.com/read/28103576/a-new-model-of-multi-visceral-and-bone-metastatic-prostate-cancer-with-perivascular-niche-targeting-by-a-novel-endothelial-specific-adenoviral-vector
#3
Zhi Hong Lu, Sergey Kaliberov, Rebecca E Sohn, Lyudmila Kaliberova, Yingqiu Du, Julie L Prior, Daniel J Leib, Anne Chauchereau, Jennifer K Sehn, David T Curiel, Jeffrey M Arbeit
While modern therapies for metastatic prostate cancer (PCa) have improved survival they are associated with an increasingly prevalent entity, aggressive variant PCa (AVPCa), lacking androgen receptor (AR) expression, enriched for cancer stem cells (CSCs), and evidencing epithelial-mesenchymal plasticity with a varying extent of neuroendocrine transdifferentiation. Parallel work revealed that endothelial cells (ECs) create a perivascular CSC niche mediated by juxtacrine and membrane tethered signaling. There is increasing interest in pharmacological metastatic niche targeting, however, targeted access has been impossible...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102558/concise-reviews-regeneration-in-mammalian-cochlea-hair-cells-help-from-supporting-cells-transdifferentiation
#4
Bénédicte Franco, Brigitte Malgrange
It is commonly assumed that mammalian cochlear cells do not regenerate. Therefore, if hair cells are lost following an injury, no recovery could occur. However, during the first postnatal week, mice harbor some progenitor cells that retain the ability to give rise to new hair cells. These progenitor cells are in fact supporting cells. Upon hair cells loss, those cells are able to generate new hair cells both by direct transdifferentiation or following cell cycle re-entry and differentiation. However, this property of supporting cells is progressively lost after birth...
January 19, 2017: Stem Cells
https://www.readbyqxmd.com/read/28101909/efficient-transdifferentiation-of-human-dermal-fibroblasts-into-skeletal-muscle
#5
Selwa Mokhtar Boularaoui, Khaled M A Abdel-Raouf, Noaf Salah Ali Alwahab, Megan E Kondash, George A Truskey, Jeremy Choon Meng Teo, Nicolas Christoforou
Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused due to severe injury, congenital defects, or tumor ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28101343/effect-of-1-25-oh-2d3-on-transdifferentiation-of-rat-renal-tubular-epithelial-cells-induced-by-high-glucose
#6
Hongtao Hu, Shen Xu, Shuang Hu, Yue Gao, Hua Shui
Deficiency in vitamin D and its active metabolite is a characteristic of chronic kidney diseases (CKDs). Previous studies have reported that 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active form of vitamin D, can attenuate renal interstitial fibrosis. The present study aimed to explore the effect of 1,25(OH)2D3 on the transdifferentiation of NRK-52E rat renal tubular epithelial cells (RTECs) induced by high glucose, as well as the expression of vitamin D receptor (VDR) and production of angiotensin (Ang) II...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28101026/transdifferentiation-of-small-cell-carcinoma-of-the-urinary-bladder-from-urothelial-carcinoma-after-transurethral-resection-of-a-bladder-tumor-intravesical-bacillus-calmette-guerin-instillation-and-chemotherapy-a-case-report
#7
Kento Morozumi, Shunichi Namiki, Takashi Kudo, Masataka Aizawa, Naomasa Ioritani, Kazuhiro Sakamoto, Yasuhiro Nakamura
A 73-year-old male underwent transurethral resection of a bladder tumor in August 2010 and April 2011. Pathological examination revealed urothelial carcinoma. After the surgery, chemotherapy and intravesical Bacillus Calmette-Guerin instillation were performed. In September 2014, he once again underwent transurethral resection of the bladder tumor for recurrence, and was again diagnosed with urothelial carcinoma, pT2, by pathological examination. After neoadjuvant chemotherapy, radical cystectomy for tumor recurrence was performed...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28100871/in-vivo-direct-reprogramming-of-liver-cells-to-insulin-producing-cells-by-virus-free-overexpression-of-defined-factors
#8
Xiao-Fei Yang, Li-Wei Ren, Lu Yang, Chun-Yan Deng, Fu-Rong Li
Direct reprogramming of autologous cells from diabetes patients to insulin producing cells is a new method for pancreatic cell replacement therapy. At present, transdifferentiation among mature cells is achieved mainly by introducing foreign genes into the starting tissue with viral vector, but there are potentical safety problems. In the present study, we delivered plasmids carrying Pdx1, Neurog3 and MafA genes (PNM) into mouse hepatocytes by hydrodynamics tail vein injection, investigated islet β cells markers in transfected cells from protein and mRNA level, and then observed the long-term control of blood glucose in diabetic mice...
January 18, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/28096214/cartilage-to-bone-transformation-during-fracture-healing-is-coordinated-by-the-invading-vasculature-and-induction-of-the-core-pluripotency-genes
#9
Diane P Hu, Federico Ferro, Frank Yang, Aaron J Taylor, Wenhan Chang, Theodore Miclau, Ralph S Marcucio, Chelsea S Bahney
Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ)...
January 15, 2017: Development
https://www.readbyqxmd.com/read/28088466/teneurin-2-tenm2-deficiency-induces-ucp1-expression-in-differentiating-human-fat-cells
#10
D Tews, T Fromme, M Keuper, S M Hofmann, K M Debatin, M Klingenspor, M Wabitsch, P Fischer-Posovszky
Under certain conditions UCP1 expressing adipocytes arise in white adipose tissue depots of both mice and humans. It is still not fully understood whether these cells differentiate de novo from specific progenitor cells or if they transdifferentiate from mature white adipocytes. Performing expression pattern analysis comparing adipocyte progenitor cells from deep and subcutaneous neck adipose tissue, we recently identified teneurin-2 (TENM2) enriched in white adipocyte progenitor cells. Here we tested whether TENM2 deficiency in adipocyte progenitor cells would lead to a brown adipocyte phenotype...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28086885/harnessing-the-early-post-injury-inflammatory-responses-for-cardiac-regeneration
#11
REVIEW
Bill Cheng, H C Chen, I W Chou, Tony W H Tang, Patrick C H Hsieh
Cardiac inflammation is considered by many as the main driving force in prolonging the pathological condition in the heart after myocardial infarction. Immediately after cardiac ischemic injury, neutrophils are the first innate immune cells recruited to the ischemic myocardium within the first 24 h. Once they have infiltrated the injured myocardium, neutrophils would then secret proteases that promote cardiac remodeling and chemokines that enhance the recruitment of monocytes from the spleen, in which the recruitment peaks at 72 h after myocardial infarction...
January 13, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28081379/direct-gingival-fibroblast-osteoblast-transdifferentiation-via-epigenetics
#12
Y Cho, B Kim, H Bae, W Kim, J Baek, K Woo, G Lee, Y Seol, Y Lee, Y Ku, I Rhyu, H Ryoo
Alveolar bone resorption caused by trauma or periodontal diseases has represented a challenge for both dental clinicians and researchers. In this study, we evaluate the osteogenic potential of human gingival fibroblasts (HGFs) through a direct transdifferentiation from HGFs to functional osteoblasts via epigenetic modification and osteogenic signaling with bone morphogenetic protein 2 (BMP2) in vitro and in vivo. HGF treatment with 5-aza-2'-deoxycytidine (5-aza-dC) induced demethylation in the hypermethylated CpG islands of the osteogenic lineage marker genes RUNX2 and ALP, and subsequent BMP2 treatment successfully drove the fibroblasts to the osteoblasts' lineage...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28079577/transdifferentiation-of-neuroendocrine-cells-gangliocytoma-associated-with-two-pituitary-adenomas-of-different-lineage-in-men1
#13
Camille Sergeant, Christel Jublanc, Delphine Leclercq, Anne-Laure Boch, Franck Bielle, Gerald Raverot, Adrian F Daly, Jacqueline Trouillas, Chiara Villa
Gangliocytomas are rare and benign neuronal cell tumors, mostly found in the hypothalamic and sellar regions. Their histogenesis is still the subject of discussions. Herein we present a unique case of a pituitary gangliocytoma associated with a prolactinoma and a corticotroph adenoma in a patient affected by MEN1. The histologic study revealed shared features between adenomatous and neuronal cells, supporting the etiological hypothesis of a common origin or a phenomenon of transdifferentiation. Furthermore, gangliocytoma could be a new tumor related to MEN1...
January 10, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28079576/mixed-gangliocytoma-pituitary-adenoma-insights-on-the-pathogenesis-of-a-rare-sellar-tumor
#14
M Beatriz S Lopes, Emily Sloan, Julie Polder
Gangliocytomas originating in the sellar region are rare; most are tumors composed of gangliocytic and pituitary adenomatous elements, forming the so-called mixed gangliocytoma-pituitary adenoma. The majority of mixed gangliocytoma adenomas are associated with endocrinopathies, mainly acromegaly and less often Cushing disease and hyperprolactinemia. In the present study, 10 cases of mixed gangliocytoma and somatotroph adenomas were evaluated for patterns of cellular differentiation and expression of lineage-specific transcription factors...
January 10, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28078070/stem-cells-and-tissue-niche-two-faces-of-the-same-coin-of-muscle-regeneration
#15
Bianca Maria Scicchitano, Gigliola Sica, Antonio Musarò
Capacity of adult muscle to regenerate in response to injury stimuli represents an important homeostatic process. Regeneration is a highly coordinated program that partially recapitulates the embryonic developmental program. However, muscle regeneration is severely compromised in several pathological conditions. It is likely that the restricted tissue repair program under pathological conditions is due to either progressive loss of stem cell populations or to missing signals that limit the damaged tissues to efficiently activate a regenerative program...
September 15, 2016: European Journal of Translational Myology
https://www.readbyqxmd.com/read/28074931/eid3-directly-associates-with-dnmt3a-during-transdifferentiation-of-human-umbilical-cord-mesenchymal-stem-cells-to-npc-like-cells
#16
Liang Luo, Wen-Jin Chen, James Q Yin, Ru-Xiang Xu
There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28074631/transdifferentiation-of-human-dermal-fibroblasts-to-smooth-muscle-like-cells-to-study-the-effect-of-myh11-and-acta2-mutations-in-aortic-aneurysms
#17
Kak K Yeung, Natalija Bogunovic, Niels Keekstra, Adriaan A M Beunders, Jorrit Pals, Kim van der Kuij, Eline Overwater, Willem Wisselink, Jan D Blankensteijn, Victor W M van Hinsbergh, Rene J P Musters, Gerard Pals, Dimitra Micha, Behrouz Zandieh-Doulabi
Mutations in genes encoding proteins of the smooth muscle cell (SMC) contractile apparatus contribute to familial aortic aneurysms. To investigate the pathogenicity of these mutations, SMC are required. We demonstrate a novel method to generate SMC-like cells from human dermal fibroblasts by transdifferentiation to study the effect of variants in genes encoding proteins of the SMC contractile apparatus (ACTA2 and MYH11) in patients with aortic aneurysms. Dermal fibroblasts from 7 healthy donors and cells from 7 patients with MYH11 or ACTA2 variants were transdifferentiated into SMC-like cells within a 2 week duration using 5ng/mL TGFβ1 on a scaffold containing collagen and elastin...
January 11, 2017: Human Mutation
https://www.readbyqxmd.com/read/28071742/core-transcription-factors-micrornas-and-small-molecules-drive-transdifferentiation-of-human-fibroblasts-towards-the-cardiac-cell-lineage
#18
Nicolas Christoforou, Syandan Chakraborty, Robert D Kirkton, Andrew F Adler, Russell C Addis, Kam W Leong
Transdifferentiation has been described as a novel method for converting human fibroblasts into induced cardiomyocyte-like cells. Such an approach can produce differentiated cells to study physiology or pathophysiology, examine drug interactions or toxicities, and engineer cardiac tissues. Here we describe the transdifferentiation of human dermal fibroblasts towards the cardiac cell lineage via the induced expression of transcription factors GATA4, TBX5, MEF2C, MYOCD, NKX2-5, and delivery of microRNAs miR-1 and miR-133a...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28068328/mll-enl-mediated-leukemia-initiation-at-the-interface-of-lymphoid-commitment
#19
A Ugale, P Säwén, M Dudenhöffer-Pfeifer, M Wahlestedt, G L Norddahl, D Bryder
Translocations involving the mixed lineage leukemia-1 are recurrent events in acute leukemia and associate with lymphoid (ALL), myeloid (AML) or mixed lineage (MLL) subtypes. Despite an association with ALL in humans, murine MLL fusion models are persistently restricted to AML. We here explored this issue using an inducible mixed lineage leukemia-eleven nineteen leukemia (MLL-ENL) mouse model. Although multiple progenitor cell types with myeloid potential are potent AML leukemia-initiating cells, also the earliest lymphoid progenitors were capable of initiating AML...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28062404/endothelial-to-mesenchymal-transition-contributes-to-endothelial-dysfunction-and-dermal-fibrosis-in-systemic-sclerosis
#20
Mirko Manetti, Eloisa Romano, Irene Rosa, Serena Guiducci, Silvia Bellando-Randone, Amato De Paulis, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
OBJECTIVE: Systemic sclerosis (SSc) features multiorgan fibrosis orchestrated predominantly by activated myofibroblasts. Endothelial-to-mesenchymal transition (EndoMT) is a transdifferentiation by which endothelial cells (ECs) lose their specific morphology/markers and acquire myofibroblast-like features. Here, we determined the possible contribution of EndoMT to the pathogenesis of dermal fibrosis in SSc and two mouse models. METHODS: Skin sections were immunostained for endothelial CD31 or vascular endothelial (VE)-cadherin in combination with α-smooth muscle actin (α-SMA) myofibroblast marker...
January 6, 2017: Annals of the Rheumatic Diseases
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