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cell fate determination

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https://www.readbyqxmd.com/read/29786094/a-protein-activity-assay-to-measure-global-transcription-factor-activity-reveals-determinants-of-chromatin-accessibility
#1
Bei Wei, Arttu Jolma, Biswajyoti Sahu, Lukas M Orre, Fan Zhong, Fangjie Zhu, Teemu Kivioja, Inderpreet Sur, Janne Lehtiö, Minna Taipale, Jussi Taipale
No existing method to characterize transcription factor (TF) binding to DNA allows genome-wide measurement of all TF-binding activity in cells. Here we present a massively parallel protein activity assay, active TF identification (ATI), that measures the DNA-binding activity of all TFs in cell or tissue extracts. ATI is based on electrophoretic separation of protein-bound DNA sequences from a highly complex DNA library and subsequent mass-spectrometric identification of the DNA-bound proteins. We applied ATI to four mouse tissues and mouse embryonic stem cells and found that, in a given tissue or cell type, a small set of TFs, which bound to only ∼10 distinct motifs, displayed strong DNA-binding activity...
May 21, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29784807/oocyte-stage-specific-effects-of-mtor-determine-granulosa-cell-fate-and-oocyte-quality-in-mice
#2
Jing Guo, Teng Zhang, Yueshuai Guo, Tao Sun, Hui Li, Xiaoyun Zhang, Hong Yin, Guangyi Cao, Yaoxue Yin, Hao Wang, Lanying Shi, Xuejiang Guo, Jiahao Sha, John J Eppig, You-Qiang Su
MTOR (mechanistic target of rapamycin) is a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation. Here we show that conditional knockout (cKO) of Mtor in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. cKO of Mtor in nongrowing primordial oocytes caused defective follicular development leading to progressive degeneration of oocytes and loss of granulosa cell identity coincident with the acquisition of immature Sertoli cell-like characteristics...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29782989/nadph-oxidase-2-deletion-enhances-neurogenesis-following-traumatic-brain-injury
#3
Jing Wang, Merry W Ma, Krishnan M Dhandapani, Darrell W Brann
The NADPH oxidase (NOX) enzyme family is a major source of reactive oxygen species (ROS) and contributor to the secondary pathology underlying traumatic brain injury (TBI). However, little is known about how NOX-derived ROS influences the proliferation and cell-fate determination of neural stem/progenitor cells (NSCs/NPCs) following TBI. In the current study, we found that deletion of NOX2 (NOX2-KO) significantly decreases the population of radial glia-like NSCs and neuroblasts but maintains the population of non-radial Sox2 expressing stem cells under physiological (non-injury) conditions...
May 18, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29781215/strap-deficiency-impairs-mouse-embryonic-stem-cells-lineage-commitment-through-cyp26a1-mediated-retinoic-acid-homeostasis
#4
Lin Jin, Chenbei Chang, Kevin M Pawlik, Arunima Datta, Larry M Johnson, Trung Vu, Joseph L Napoli, Pran K Datta
Retinoic acid (RA) signaling is essential for the differentiation of embryonic stem cells (ESCs) and vertebrate development. RA biosynthesis and metabolism are controlled by a series of enzymes, but the molecular regulators of these enzymes remain largely obscure. In this study, we investigated the functional role of the WD-domain protein STRAP (serine threonine kinase receptor-associated protein) in the pluripotency and lineage commitment of murine ESCs. We generated Strap knockout (KO) mouse ESCs and subjected them to spontaneous differentiation...
May 21, 2018: Stem Cells
https://www.readbyqxmd.com/read/29781103/targeting-ubiquitin-specific-protease-7-in-cancer-a-deubiquitinase-with-great-prospects
#5
REVIEW
Farjana Yeasmin Khusbu, Fang-Zhi Chen, Han-Chun Chen
Deubiquitinase (DUB)-mediated cleavage of ubiquitin chain balances ubiquitination and deubiquitination for determining protein fate. USP7 is one of the best characterized DUBs and functionally important. Numerous proteins have been identified as potential substrates and binding partners of USP7; those play crucial roles in diverse array of cellular and biological processes including tumour suppression, cell cycle, DNA repair, chromatin remodelling, and epigenetic regulation. This review aims at summarizing the current knowledge of this wide association of USP7 with many cellular processes that enlightens the possibility of abnormal USP7 activity in promoting oncogenesis and the importance of identification of specific inhibitors...
May 20, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29779895/identification-and-single-cell-functional-characterization-of-an-endodermally-biased-pluripotent-substate-in-human-embryonic-stem-cells
#6
Thomas F Allison, Andrew J H Smith, Konstantinos Anastassiadis, Jackie Sloane-Stanley, Veronica Biga, Dylan Stavish, James Hackland, Shan Sabri, Justin Langerman, Mark Jones, Kathrin Plath, Daniel Coca, Ivana Barbaric, Paul Gokhale, Peter W Andrews
Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal...
May 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29779174/correction-to-impaired-bioenergetics-in-mutant-mitochondrial-dna-determines-cell-fate-during-seizure-like-activity
#7
Stjepana Kovac, Elisavet Preza, Henry Houlden, Matthew C Walker, Andrey Y Abramov
The original version of this article unfortunately contained mistake. The author's family name "Kov ac" was written with space thus this should be corrected to "Kovac".
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29777574/factors-influencing-the-umbilical-cord-blood-stem-cell-industry-an-evolving-treatment-landscape
#8
REVIEW
Carla Dessels, Marco Alessandrini, Michael Sean Pepper
Hematopoietic stem cell transplantation (HSCT) is common practice today for life threatening malignant and non-malignant diseases of the blood and immune systems. Umbilical cord blood (UCB) is rich in hematopoietic stem cells (HSCs) and is an attractive alternative to harvesting HSCs from bone marrow or when mobilized into peripheral blood. One of the most appealing attributes of UCB is that it can be banked for future use and hence provides an off-the-shelf solution for patients in urgent need of a transplantation...
May 18, 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29775646/the-rna-binding-protein-ars2-supports-hematopoiesis-at-multiple-levels
#9
Seerat Elahi, Shawn M Egan, G Aaron Holling, Rachel L Kandefer, Michael J Nemeth, Scott H Olejniczak
Recent biochemical characterization of Arsenic resistance protein 2 (Ars2) has established it as central to determining the fate of nascent RNA polymerase II (RNAPII) transcripts. Through interactions with the nuclear 5'-7-methylguanosine (7mG) cap binding complex (CBC), Ars2 promotes co-transcriptional processing coupled with nuclear export or degradation of several classes of RNAPII transcripts, allowing for gene expression programs that facilitate rapid and sustained proliferation of immortalized cells in culture...
May 15, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29775615/extracellular-matrix-protein-dmp1-suppresses-osteogenic-differentiation-of-mesenchymal-stem-cells
#10
Shufan Zhang, Huixuan Wan, Peng Wang, Mengmeng Liu, Gongchen Li, Chunxue Zhang, Yao Sun
Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29773643/the-transcription-factor-bhlhe40-is-a-switch-of-inflammatory-versus-antiinflammatory-th1-cell-fate-determination
#11
Fang Yu, Suveena Sharma, Dragana Jankovic, Rama Krishna Gurram, Pan Su, Gangqing Hu, Rao Li, Sadiye Rieder, Keji Zhao, Bing Sun, Jinfang Zhu
Type 1 T helper (Th1) cells play a critical role in host defense against intracellular pathogens and in autoimmune diseases by producing a key inflammatory cytokine interferon (IFN)-γ; some Th1 cells can also be antiinflammatory through producing IL-10. However, the molecular switch for regulating the differentiation of inflammatory and antiinflammatory Th1 cells is still elusive. Here, we show that Bhlhe40 -deficient CD4 Th1 cells produced less IFN-γ but substantially more IL-10 than wild-type Th1 cells both in vitro and in vivo...
May 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29771958/cooperation-of-bmp-and-ihh-signaling-in-interdigital-cell-fate-determination
#12
Arunima Murgai, Sara Altmeyer, Stephanie Wiegand, Przemko Tylzanowski, Sigmar Stricker
The elaborate anatomy of hands and feet is shaped by coordinated formation of digits and regression of the interdigital mesenchyme (IM). A failure of this process causes persistence of interdigital webbing and consequently cutaneous syndactyly. Bone morphogenetic proteins (BMPs) are key inductive factors for interdigital cell death (ICD) in vivo. NOGGIN (NOG) is a major BMP antagonist that can interfere with BMP-induced ICD when applied exogenously, but its in vivo role in this process is unknown. We investigated the physiological role of NOG in ICD and found that Noggin null mice display cutaneous syndactyly and impaired interdigital mesenchyme specification...
2018: PloS One
https://www.readbyqxmd.com/read/29771299/at-the-crossroads-of-fate-somatic-cell-lineage-specification-in-the-fetal-gonad
#13
Emmi Rotgers, Anne Jørgensen, Humphrey Hung-Chang Yao
The reproductive endocrine systems are vastly different between male and female. This sexual dimorphism of endocrine milieu originates from sex-specific differentiation of the somatic cells in the gonads during fetal life. The majority of gonadal somatic cells arise from the adrenogonadal primordium. After separation of the adrenal and gonadal primordia, the gonadal somatic cells initiate sex-specific differentiation during gonadal sex determination with the specification of the supporting cell lineages: Sertoli cells in the testis vs...
May 15, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29769743/tigar-knockdown-enhanced-the-anticancer-effect-of-aescin-via-regulating-autophagy-and-apoptosis-in-colorectal-cancer-cells
#14
Bin Li, Zhong Wang, Jia-Ming Xie, Gang Wang, Li-Qiang Qian, Xue-Mei Guan, Xue-Ping Shen, Zheng-Hong Qin, Gen-Hai Shen, Xiao-Qiang Li, Quan-Gen Gao
Our previous study showed that TP53-induced glycolysis and apoptosis regulator (TIGAR) regulated ROS, autophagy, and apoptosis in response to hypoxia and chemotherapeutic drugs. Aescin, a triterpene saponin, exerts anticancer effects and increases ROS levels. The ROS is a key upstream signaling to activate autophagy. Whether there is a crosstalk between TIGAR and aescin in regulating ROS, autophagy, and apoptosis is unknown. In this study, we found that aescin inhibited cell viability and colony formation, and induced DNA damage, cell cycle arrest, and apoptosis in cancer cell lines HCT-116 and HCT-8 cells...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29769401/microinjection-of-mrnas-and-oligonucleotides
#15
Sally A Moody
Microinjecting lineage tracers into a single blastomere in the normal, intact embryo identifies the repertoire of cell types derived from it. In order to reveal the full developmental potential of that blastomere or identify the mechanisms by which its fate is determined, one needs to modify its gene expression under controlled experimental conditions. One method by which this is easily accomplished in Xenopus is by microinjecting synthetic mRNAs or antisense oligonucleotides into an identified blastomere to target altered gene expression specifically to its lineage...
May 16, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29769398/cleavage-blastomere-deletion-and-transplantation-to-test-cell-fate-commitment-in-xenopus
#16
Sally A Moody
Fate maps identify the precursors of an organ, and tracing the members of a blastomere lineage over time shows how its descendants come to populate that organ. The fates of the individual blastomeres of the two- to 32-cell Xenopus embryo have been fully mapped to reveal which cells are the major contributors to various cell types, tissues, and organs. However, because these fate maps were produced in the normal embryo, they do not reveal whether a precursor blastomere is competent to give rise to additional tissues or is already committed to its fate-mapped repertoire of descendants...
May 16, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29769394/analysis-of-cell-fate-commitment-in-xenopus-embryos
#17
Sally A Moody
The fates of individual cleavage-stage blastomeres and of groups of cells at the blastula through gastrula stages of Xenopus embryos have been mapped in great detail. These studies identified the major contributors of the three germ layers as well as a variety of tissues and organs and several specific cell types. One can use these fate maps to test the commitment of single cells or groups of cells to produce their normal repertoire of descendants, to identify the genes that regulate fate commitment, and to modulate the levels of gene expression in specific lineages to determine gene function in a variety of developmental processes...
May 16, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29769392/cleavage-blastomere-explant-culture-in-xenopus
#18
Sally A Moody
The individual blastomeres of Xenopus two- to 32-cell embryos have been fate mapped. This work identified the precursors of most of the embryonic cell types, tissues and organs; however, the maps do not reveal the cell interactions or signaling pathways that are required for establishing cell fates. This protocol describes an explant culture approach for culturing blastomeres in isolation to test whether a cell's fate has been determined. Cleavage blastomeres can be cultured in a simple salt medium without added factors because they contain intracellular yolk platelets, which provide an intrinsic energy source...
May 16, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29769320/o-glcnac-transferase-missense-mutations-linked-to-x-linked-intellectual-disability-deregulate-genes-involved-in-cell-fate-determination-and-signaling
#19
Nithya Selvan, Stephan George, Fatema J Serajee, Marie Shaw, Lynne Hobson, Vera M Kalscheuer, Nripesh Prasad, Shawn E Levy, Juliet Taylor, Salim Afitmos, Charles E Schwartz, Ahm M Huq, Jozef Gecz, Lance Wells
It is estimated that ~1% of the world's population has intellectual disability, with males affected more often than females. OGT is an X-linked gene encoding for the enzyme O-GlcNAc transferase (OGT), which carries out the reversible addition of N-Acetylglucosamine (GlcNAc) to Ser/Thr residues of its intracellular substrates. Three missense mutations in the tetratricopeptide (TPR) repeats of OGT have recently been reported to cause X-linked Intellectual Disability (XLID). Here we report the discovery of two additional novel missense mutations (c...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29767511/low-dose-arsenic-trioxide-modulates-the-differentiation-of-mouse-embryonic-stem-cells
#20
Wenlin Yuan, Jun Chen, Hongren Huang, Zhihui Cai, Qinjie Ling, Feng Huang, Zhi Huang
Arsenic (As) is a well-known environmental pollutant,while arsenic trioxide (ATO) has been proven to be an effective treatment for acute promyelocytic leukemia, however, the mechanism underlying its dual effects is not fully understood.Embryonic stem cells (ESCs) appear properties of stemness and serve as a popular model to investigate epigenetic modifiers includingenvironmental pollutants.Herein, the effect of low dose ATO on differentiation were evaluatedin vitro using a mouse ESCs (mESCs) cell line, CGR8...
May 16, 2018: Chemical Research in Toxicology
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