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https://www.readbyqxmd.com/read/28813672/chromatin-and-transcriptional-analysis-of-mesoderm-progenitor-cells-identifies-hopx-as-a-regulator-of-primitive-hematopoiesis
#1
Nathan J Palpant, Yuliang Wang, Brandon Hadland, Rebecca J Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR(+)/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813665/lineage-restricted-mammary-stem-cells-sustain-the-development-homeostasis-and-regeneration-of-the-estrogen-receptor-positive-lineage
#2
Alexandra Van Keymeulen, Marco Fioramonti, Alessia Centonze, Gaëlle Bouvencourt, Younes Achouri, Cédric Blanpain
The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER)(+) and ER(-) cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER(+) lineage is maintained by multipotent SCs or by lineage-restricted SCs...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813430/reprogramming-human-gallbladder-cells-into-insulin-producing-%C3%AE-like-cells
#3
Feorillo Galivo, Eric Benedetti, Yuhan Wang, Carl Pelz, Jonathan Schug, Klaus H Kaestner, Markus Grompe
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28813413/polylox-barcoding-reveals-haematopoietic-stem-cell-fates-realized-in-vivo
#4
Weike Pei, Thorsten B Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28811863/long-noncoding-rnas-and-rna-binding-proteins-in-oxidative-stress-cellular-senescence-and-age-related-diseases
#5
REVIEW
Chongtae Kim, Donghee Kang, Eun Kyung Lee, Jae-Seon Lee
Cellular senescence is a complex biological process that leads to irreversible cell-cycle arrest. Various extrinsic and intrinsic insults are associated with the onset of cellular senescence and frequently accompany genomic or epigenomic alterations. Cellular senescence is believed to contribute to tumor suppression, immune response, and tissue repair as well as aging and age-related diseases. Long noncoding RNAs (lncRNAs) are >200 nucleotides long, poorly conserved, and transcribed in a manner similar to that of mRNAs...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811345/inhibitors-of-the-histone-methyltransferases-ezh2-1-induce-a-potent-antiviral-state-and-suppress-infection-by-diverse-viral-pathogens
#6
Jesse H Arbuckle, Paul J Gardina, David N Gordon, Heather D Hickman, Jonathan W Yewdell, Theodore C Pierson, Timothy G Myers, Thomas M Kristie
Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811311/linking-the-environment-daf-7-tgf%C3%AE-signaling-and-lag-2-dsl-ligand-expression-in-the-germline-stem-cell-niche
#7
Olga Pekar, Maria C Ow, Kailyn Y Hui, Marcus B Noyes, Sarah E Hall, E Jane Albert Hubbard
The developmental accumulation of proliferative germ cells in the C. elegans hermaphrodite is sensitive to the organismal environment. Previously, we found that the TGFβ signaling pathway links the environment and proliferative germ cell accumulation. Neuronal DAF-7/TGFβ causes a DAF-1/TGFβR signaling cascade in the gonadal distal tip cell (DTC), the germline stem cell niche, where it negatively regulates a DAF-3 SMAD and DAF-5 Sno-Ski. LAG-2, a founding DSL ligand family member, is produced in the DTC and activates the GLP-1/Notch receptor on adjacent germ cells to maintain germline stem cell fate...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28811310/live-fate-mapping-of-joint-associated-fibroblasts-visualizes-expansion-of-cell-contributions-during-zebrafish-fin-regeneration
#8
Valerie A Tornini, John D Thompson, Raymond L Allen, Kenneth D Poss
The blastema is a mass of progenitor cells responsible for regeneration of amputated salamander limbs and fish fins. Previous studies have indicated that resident cell sources producing the blastema contribute lineage-restricted progeny to regenerating tissue. However, these studies have labeled general cell types rather than granular cell subpopulations, and they do not explain the developmental transitions that must occur for distal structures to arise from cells with proximal identities in the appendage stump...
August 15, 2017: Development
https://www.readbyqxmd.com/read/28811218/wnt-signaling-positively-regulates-endothelial-cell-fate-specification-in-the-fli1a-positive-progenitor-population-via-lef1
#9
Kathleen Hübner, Kathrin S Grassme, Jyoti Rao, Nina K Wenke, Cordula L Zimmer, Laura Korte, Katja Mu Ller, Saulius Sumanas, Boris Greber, Wiebke Herzog
During vertebrate embryogenesis, vascular endothelial cells (ECs) and primitive erythrocytes become specified within close proximity in the posterior lateral plate mesoderm (LPM) from a common progenitor. However, the signaling cascades regulating the specification into either lineage remain largely elusive. Here, we analyze the contribution of β-catenin dependent Wnt signaling to EC and erythrocyte specification during zebrafish embryogenesis. We generated novel β-catenin dependent Wnt signaling reporters which, by using destabilized fluorophores (Venus-Pest, dGFP), specifically allow us to detect Wnt signaling responses in narrow time windows as well as in spatially restricted domains, defined by Cre recombinase expression (Tg(axin2BAC:Venus-Pest)(mu288); Tg(14TCF:loxP-STOP-loxP-dGFP)(mu202))...
August 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28809839/a-novel-mammary-fat-pad-transplantation-technique-to-visualize-the-vessel-generation-of-vascular-endothelial-stem-cells
#10
Qing Cissy Yu, Wenqian Song, Dengwen Lai, Yi Arial Zeng
Endothelial cells (ECs) are the fundamental building blocks of the vascular architecture and mediate vascular growth and remodeling to ensure proper vessel development and homeostasis. However, studies on endothelial lineage hierarchy remain elusive due to the lack of tools to gain access as well as to directly evaluate their behavior in vivo. To address this shortcoming, a new tissue model to study angiogenesis using the mammary fat pad has been developed. The mammary gland develops mostly in the postnatal stages, including puberty and pregnancy, during which robust epithelium proliferation is accompanied by extensive vascular remodeling...
August 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28808919/backbone-and-side-chain-assignments-of-the-second-rna-binding-domain-of-musashi-1-in-its-free-form-and-in-complex-with-5-mer-rna
#11
Ryo Iwaoka, Takashi Nagata, Kengo Tsuda, Takao Imai, Hideyuki Okano, Naohiro Kobayashi, Masato Katahira
Musashi1 (Msi1) is an RNA-binding protein that is involved in cell fate determination. Here, we report the (1)H, (15)N, and (13)C resonance assignments of Msi1 second RNA-binding domain in free form and in complex with RNA. The assignments can be utilized for NMR structure and dynamics analyses of the Msi1:RNA complex, and moreover, for chemical shift perturbation analyses to evaluate the binding of potential small molecule inhibitors against Msi1:RNA interaction.
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28808415/foxo-signaling-pathways-as-therapeutic-targets-in-cancer
#12
REVIEW
Mohd Farhan, Haitao Wang, Uma Gaur, Peter J Little, Jiangping Xu, Wenhua Zheng
Many transcription factors play a key role in cellular differentiation and the delineation of cell phenotype. Transcription factors are regulated by phosphorylation, ubiquitination, acetylation/deacetylation and interactions between two or more proteins controlling multiple signaling pathways. These pathways regulate different physiological processes and pathological events, such as cancer and other diseases. The Forkhead box O (FOXO) is one subfamily of the fork head transcription factor family with important roles in cell fate decisions and this subfamily is also suggested to play a pivotal functional role as a tumor suppressor in a wide range of cancers...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28808338/a-dynamical-framework-for-complex-fractional-killing
#13
Richard Ballweg, Andrew L Paek, Tongli Zhang
When chemotherapy drugs are applied to tumor cells with the same or similar genotypes, some cells are killed, while others survive. This fractional killing contributes to drug resistance in cancer. Through an incoherent feedforward loop, chemotherapy drugs not only activate p53 to induce cell death, but also promote the expression of apoptosis inhibitors which inhibit cell death. Consequently, cells in which p53 is activated early undergo apoptosis while cells in which p53 is activated late survive. The incoherent feedforward loop and the essential role of p53 activation timing makes fractional killing a complex dynamical challenge, which is hard to understand with intuition alone...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808228/loss-of-usp9x-disrupts-cell-adhesion-and-components-of-the-wnt-and-notch-signaling-pathways-in-neural-progenitors
#14
Susitha Premarathne, Mariyam Murtaza, Nicholas Matigian, Lachlan A Jolly, Stephen A Wood
Development of neural progenitors depends upon the coordination of appropriate intrinsic responses to extrinsic signalling pathways. Here we show the deubiquitylating enzyme, Usp9x regulates components of both intrinsic and extrinsic fate determinants. Nestin-cre mediated ablation of Usp9x from embryonic neural progenitors in vivo resulted in a transient disruption of cell adhesion and apical-basal polarity and, an increased number and ectopic localisation of intermediate neural progenitors. In contrast to other adhesion and polarity proteins, levels of β-catenin protein, especially S33/S37/T41 phospho-β-catenin, were markedly increased in Usp9x (-/Y) embryonic cortices...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808191/shunts-channels-and-lipoprotein-endosomal-traffic-a-new-model-of-cholesterol-homeostasis-in-the-hepatocyte
#15
Robert Scott Kiss, Allan Sniderman
The liver directs cholesterol metabolism in the organism. All the major fluxes of cholesterol within the body involve the liver: dietary cholesterol is directed to the liver; cholesterol from peripheral cells goes to the liver; the liver is a major site of cholesterol synthesis for the organism; cholesterol is secreted from the liver within the bile, within apoB lipoproteins and translocated to nascent HDL. The conventional model of cholesterol homeostasis posits that cholesterol from any source enters a common, rapidly exchangeable pool within the cell, which is in equilibrium with a regulatory pool...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807898/hypothalamic-sonic-hedgehog-is-required-for-cell-specification-and-proliferation-of-lhx3-lhx4-pituitary-embryonic-precursors
#16
G Carreno, J Apps, E J Lodge, L Panousopoulos, S Haston, J M Gonzalez-Meljem, H Hahn, C L Andoniadou, J P Martinez-Barbera
Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28807896/fgf10-progenitors-give-rise-to-the-chick-hypothalamus-by-rostral-and-caudal-growth-and-differentiation
#17
Travis Fu, Matthew Towers, Marysia Placzek
Classical descriptions of the hypothalamus divide it into three rostro-caudal domains but little is known about their embryonic origins. To investigate this we performed targeted fate-mapping, molecular characterisation and cell cycle analyses in the embryonic chick. Presumptive hypothalamic cells derive from the rostral diencephalic ventral midline, lie above the prechordal mesendoderm and express Fgf10Fgf10(+) progenitors undergo anisotropic growth: those displaced rostrally differentiate into anterior cells, then those displaced caudally differentiate into mammillary cells...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28807012/protein-deubiquitinase-usp7-is-required-for-osteogenic-differentiation-of-human-adipose-derived-stem-cells
#18
Yiman Tang, Longwei Lv, Wenyue Li, Xiao Zhang, Yong Jiang, Wenshu Ge, Yongsheng Zhou
BACKGROUND: Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with self-renewal capabilities and multilineage differentiation potential, including osteogenesis. Although protein deubiquitinases have been linked to stem cell fate determination, whether protein deubiquitination contributes to lineage commitment during osteogenic differentiation of hASCs remains to be investigated. The objective of this study was to evaluate the effects of the ubiquitin specific protease 7 (USP7) on osteogenic differentiation of hASCs...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28805814/cerebellar-granule-cell-replenishment-postinjury-by-adaptive-reprogramming-of-nestin-progenitors
#19
Alexandre Wojcinski, Andrew K Lawton, N Sumru Bayin, Zhimin Lao, Daniel N Stephen, Alexandra L Joyner
Regeneration of several organs involves adaptive reprogramming of progenitors, but the intrinsic capacity of the developing brain to replenish lost cells remains largely unknown. Here we found that the developing cerebellum has unappreciated progenitor plasticity, since it undergoes near full growth and functional recovery following acute depletion of granule cells, the most plentiful neuron population in the brain. We demonstrate that following postnatal ablation of granule cell progenitors, Nestin-expressing progenitors, specified during mid-embryogenesis to produce astroglia and interneurons, switch their fate and generate granule neurons in mice...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28804501/regulatory-role-of-redox-balance-in-determination-of-neural-precursor-cell-fate
#20
REVIEW
Mohamed Ariff Iqbal, Eftekhar Eftekharpour
In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS) reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes...
2017: Stem Cells International
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