somatic tissue
Recently Published Documents


TOTAL DOCUMENTS

226
(FIVE YEARS 57)

H-INDEX

31
(FIVE YEARS 4)

2022 ◽  
Author(s):  
Imge Ozugergin ◽  
Karina Mastronardi ◽  
Chris Law ◽  
Alisa Piekny

Cytokinesis occurs at the end of mitosis due to the ingression of a contractile ring that cleaves the daughter cells. The core machinery regulating this crucial process is conserved among metazoans. Multiple pathways control ring assembly, but their contribution in different cell types is not known. We found that in the C. elegans embryo, AB and P1 cells fated to be somatic tissue and germline, respectively, have different cytokinesis kinetics supported by distinct myosin levels and organization. Through perturbation of RhoA or polarity regulators and the generation of tetraploid strains, we found that ring assembly is controlled by multiple fate-dependent factors that include myosin-levels, and mechanisms that respond to cell size. Active Ran coordinates ring position with the segregating chromatids in HeLa cells by forming an inverse gradient with importins that control the cortical recruitment of anillin. We found that the Ran pathway regulates anillin in AB cells, but functions differently in P1 cells. We propose that ring assembly delays in P1 cells caused by low myosin and Ran signaling coordinate the timing of ring closure with their somatic neighbours.


Author(s):  
Ivo Ngundu Woogeng ◽  
Bogumil Kaczkowski ◽  
Imad Abugessaisa ◽  
Haiming Hu ◽  
Akihiro Tachibana ◽  
...  

2021 ◽  
Vol 22 (24) ◽  
pp. 13623
Author(s):  
Braulio Valdebenito-Maturana ◽  
Cristina Guatimosim ◽  
Mónica Alejandra Carrasco ◽  
Juan Carlos Tapia

Spatial transcriptomics (ST) is transforming the way we can study gene expression and its regulation through position-specific resolution within tissues. However, as in bulk RNA-Seq, transposable elements (TEs) are not being studied due to their highly repetitive nature. In recent years, TEs have been recognized as important regulators of gene expression, and thus, TE expression analysis in a spatially resolved manner could further help to understand their role in gene regulation within tissues. We present SpatialTE, a tool to analyze TE expression from ST datasets and show its application in somatic and diseased tissues. The results indicate that TEs have spatially regulated expression patterns and that their expression profiles are spatially altered in ALS disease, indicating that TEs might perform differential regulatory functions within tissue organs. We have made SpatialTE publicly available as open-source software under an MIT license.


2021 ◽  
Author(s):  
Verena Koerber ◽  
Naser Ansari-Pour ◽  
Niels Asger Jakobsen ◽  
Rachel Moore ◽  
Nina Claudino ◽  
...  

Dividing somatic stem cells acquire DNA changes marking different clones. With time, clones can become large, either stochastically through neutral drift, or increased fitness and consequent selection. We present a simple, direct, and general approach that distinguishes between these two processes in normal somatic tissue in individuals. The method relies on single time point whole genome sequencing to study somatic mosaicism as tissues age. Using this method, we show that in human clonal hemopoiesis (CH), clones with CH driver mutations, that comprise a median of 24% of hematopoiesis originate decades before they are detected. They expand, through selection by a median of 26% per year. Overall, there is a 3-fold increased rate of stem cell division and an 8.6-fold increase in active long-term stem cells.


2021 ◽  
Author(s):  
Lejon Kralemann ◽  
Sylvia de Pater ◽  
Hexi Shen ◽  
Susan Kloet ◽  
Robin van Schendel ◽  
...  

Abstract Agrobacterium tumefaciens, a pathogenic bacterium capable of transforming plants through horizontal gene transfer, is nowadays the preferred vector for plant genetic engineering. The vehicle for transfer is the T-strand, a single-stranded DNA molecule bound by the bacterial protein VirD2, which guides T-DNA into the plants nucleus where it integrates. How VirD2 is removed from T-DNA, and which mechanism acts to attach the liberated end to the plant genome is currently unknown. Here, using newly developed technology that yields hundreds of T-DNA integrations in somatic tissue of Arabidopsis thaliana, we uncover two redundant mechanisms for the genomic capture of the T-DNA’s 5’ end. Different from capture of the 3’ end of the T-DNA, which is the exclusive action of polymerase theta-mediated end joining (TMEJ), 5’ attachment is accomplished either by TMEJ or by canonical non-homologous end joining (cNHEJ). We further find that TMEJ needs MRE11, whereas cNHEJ requires TDP2 to remove the 5’-end blocking protein VirD2. As a consequence, T-DNA integration is severely impaired in plants deficient for both MRE11 and TDP2 (or other cNHEJ factors). In support of MRE11 and cNHEJ specifically acting on the 5’ end, we demonstrate rescue of the integration defect of double-deficient plants by using T-DNAs that are capable of forming telomeres upon 3’ capture. Our study provides a mechanistic model for how Agrobacterium exploits the plant’s own DNA repair machineries to transform them.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Li Zhang ◽  
Lu Liu ◽  
Zhiqiu Zhong ◽  
Hengfang Jin ◽  
Jian Jia ◽  
...  

Abstract Background Suboptimal tissue perfusion and oxygenation may be the root cause of certain perioperative complications in neonates and infants having complicated aortic coarctation repair. Practical, effective, and real-time monitoring of organ perfusion and/or tissue oxygenation may provide early warning of end-organ mal-perfusion. Methods Neonates/infants who were scheduled for aortic coarctation repair with cardiopulmonary bypass (CPB) and selective cerebral perfusion (SCP) from January 2015 to February 2017 in Children’s Hospital of Nanjing Medical University participated in this prospective observational study. Cerebral and somatic tissue oxygen saturation (SctO2 and SstO2) were monitored on the forehead and at the thoracolumbar paraspinal region, respectively. SctO2 and SstO2 were recorded at different time points (baseline, skin incision, CPB start, SCP start, SCP end, aortic opening, CPB end, and surgery end). SctO2 and SstO2 were correlated with mean arterial pressure (MAP) and partial pressure of arterial blood carbon dioxide (PaCO2). Results Data of 21 patients were analyzed (age=75±67 days, body weight=4.4±1.0 kg). SstO2 was significantly lower than SctO2 before aortic opening and significantly higher than SctO2 after aortic opening. SstO2 correlated with leg MAP when the measurements during SCP were (r=0.67, p<0.0001) and were not included (r=0.46, p<0.0001); in contrast, SctO2 correlated with arm MAP only when the measurements during SCP were excluded (r=0.14, p=0.08 vs. r=0.66, p<0.0001). SCP also confounded SctO2/SstO2’s correlation with PaCO2; when the measurements during SCP were excluded, SctO2 positively correlated with PaCO2 (r=0.65, p<0.0001), while SstO2 negatively correlated with PaCO2 (r=-0.53, p<0.0001). Conclusions SctO2 and SstO2 have distinct patterns of changes before and after aortic opening during neonate/infant aortic coarctation repair. SctO2/SstO2’s correlations with MAP and PaCO2 are confounded by SCP. The outcome impact of combined SctO2/SstO2 monitoring remains to be studied.


2021 ◽  
pp. 1677-1686
Author(s):  
Alison N. Schwartz ◽  
Sophie R. Hyman ◽  
Samantha M. Stokes ◽  
Danielle Castillo ◽  
Nadine M. Tung ◽  
...  

PURPOSE Multigene panel testing (MGPT) identifies TP53 pathogenic or likely pathogenic (P/LP) variants in patients with diverse phenotypes, of which only one is classic Li-Fraumeni syndrome. Low variant allelic fraction (VAF) in TP53 found on germline testing may suggest aberrant clonal expansion or constitutional mosaicism. We evaluated TP53-positive probands seen in a cancer genetics program to determine germline versus somatic status. METHODS We reviewed TP53-positive probands from 2012 to 2019 identified by MGPT on blood or saliva (N = 84). Available VAFs were collected. Probands with a familial variant, who met Li-Fraumeni syndrome testing criteria or who carried a founder variant, were considered germline. For those with uncertain germline status, TP53 variants were further examined using ancillary data of family members and somatic tissue. RESULTS Of the 84 probands, 54.7% had germline variants with 33.3% meeting criteria for germline status and 21.4% confirmed through ancillary testing. Aberrant clonal expansion comprised 13.1% with clonal hematopoiesis of indeterminate potential and 2.4% with a hematologic malignancy. Constitutional mosaicism was confirmed in 8.3% probands. Definitive status could not be determined in 3.6% despite ancillary assessment, and 17.9% did not have ancillary testing. CONCLUSION A TP53 P/LP variant found on peripheral blood or saliva MGPT does not always originate in the germline. In a clinical cancer genetics cohort, approximately half of the patients had TP53 P/LP germline variants; these patients plus those with constitutional mosaicism require intensified surveillance. A framework of multiple strategies enables discernment of germline from constitutional mosaic and acquired variants, which is essential for appropriate management.


Author(s):  
Kelvin Pieknell ◽  
Yanuar Alan Sulistio ◽  
Noviana Wulansari ◽  
Wahyu Handoko Wibowo Darsono ◽  
Mi-Yoon Chang ◽  
...  

2021 ◽  
Author(s):  
Fei Guo ◽  
Shuaiying Jia ◽  
Qiyan Wang ◽  
Qinyu Liu ◽  
Mingquan Hu ◽  
...  

Abstract Background: Intraoperative cerebral desaturations have been associated with worse neurological outcomes after supine surgery. However, it is not clear whether intraoperative somatic tissue oxygenation is more associated with postoperative cognitive dysfunction (POCD) than cerebral oxygenation in patients with hypertension after prone spine surgery.Methods: Patients with hypertension scheduled for spine open surgery were included from 2020 to 2021 in a single-center, prospective, observational study. Baseline both cerebral and somatic tissue oxygen saturation were measured in operating room before surgery. Cerebral and somatic tissue oxygen saturations were monitored continuously throughout surgery. The presence of POCD was assessed using the Mini-Mental Status Examination (MMSE). Association with POCD was evaluated with unadjusted analyses and multivariable logistic regression.Results: One hundred and one of 112 patients were included, and 28 (27.8%) developed POCD. None of the investigated SctO2 variables was predictive of POCD. On the contrary, the patients with POCD had a higher decrease in intraoperative absolute SstO2 decrease and relative SstO2 decrease compared with the patients without POCD (4.9%±3.8% vs. 3.6%±2.6%, P=0.037; 7.4%±5.6% vs. 5.3%±3.8%, P=0.036; respectively). Finally, three SstO2 parameters respectively were associated with POCD, including a higher absolute SstO2 decrease (OR, 1.223; 95%CI, 1.031-1.451; P=0.021), a higher absolute SstO2 decrease (OR, 1.138; 95%CI, 1.011-1.281; P=0.032) and falling below 90% of baseline SstO2 (OR, 11.388; 95%CI, 2.367-54.785; P=0.002), independent of ASA III, preoperative platelet and postoperative sepsis. Conclusions: Twenty-eight (27.8%) of 101patients developed POCD. Somatic tissue oxygenation has a stronger association with POCD than cerebral tissue oxygenation after spine open surgery in patients with hypertension.Clinical trial registration: ChiCTR1900028392. Registered 20 December 2019.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marion Pierre ◽  
Mohammed Djemai ◽  
Hugo Poulin ◽  
Mohamed Chahine

AbstractCardiomyocytes derived from patient-specific induced pluripotent stem cells (iPSC-CMs) successfully reproduce the mechanisms of several channelopathies. However, this approach involve cell reprogramming from somatic tissue biopsies or genomic editing in healthy iPSCs for every mutation found and to be investigated. We aim to knockout (KO) NaV1.5, the cardiac sodium channel, in a healthy human iPSC line, characterize the model and then, use it to express variants of NaV1.5. We develop a homozygous NaV1.5 KO iPSC line able to differentiate into cardiomyocytes with CRISPR/Cas9 tool. The NaV1.5 KO iPSC-CMs exhibited an organized contractile apparatus, spontaneous contractile activity, and electrophysiological recordings confirmed the major reduction in total Na+ currents. The action potentials (APs) exhibited a reduction in their amplitude and in their maximal rate of rise. Voltage optical mapping recordings revealed that the conduction velocity Ca2+ transient waves propagation velocities were slow. A wild-type (WT) NaV1.5 channel expressed by transient transfection in the KO iPSC-CMs restored Na+ channel expression and AP properties. The expression of NaV1.5/delQKP, a long QT type 3 (LQT3) variant, in the NaV1.5 KO iPSC-CMs showed that dysfunctional Na+ channels exhibited a persistent Na+ current and caused prolonged AP duration that led to arrhythmic events, characteristics of LQT3.


Sign in / Sign up

Export Citation Format

Share Document