Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections, and comprise nearly 8% of the human genome. The most recently acquired human ERV is HERVK(HML-2), which repeatedly ...infected the primate lineage both before and after the divergence of the human and chimpanzee common ancestor. Unlike most other human ERVs, HERVK retained multiple copies of intact open reading frames encoding retroviral proteins. However, HERVK is transcriptionally silenced by the host, with the exception of in certain pathological contexts such as germ-cell tumours, melanoma or human immunodeficiency virus (HIV) infection. Here we demonstrate that DNA hypomethylation at long terminal repeat elements representing the most recent genomic integrations, together with transactivation by OCT4 (also known as POU5F1), synergistically facilitate HERVK expression. Consequently, HERVK is transcribed during normal human embryogenesis, beginning with embryonic genome activation at the eight-cell stage, continuing through the emergence of epiblast cells in preimplantation blastocysts, and ceasing during human embryonic stem cell derivation from blastocyst outgrowths. Remarkably, we detected HERVK viral-like particles and Gag proteins in human blastocysts, indicating that early human development proceeds in the presence of retroviral products. We further show that overexpression of one such product, the HERVK accessory protein Rec, in a pluripotent cell line is sufficient to increase IFITM1 levels on the cell surface and inhibit viral infection, suggesting at least one mechanism through which HERVK can induce viral restriction pathways in early embryonic cells. Moreover, Rec directly binds a subset of cellular RNAs and modulates their ribosome occupancy, indicating that complex interactions between retroviral proteins and host factors can fine-tune pathways of early human development.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is ...challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential-the number of expressed genes per cell-and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies.
During development, cells progress from a pluripotent state to a more restricted fate within a particular germ layer. However, cranial neural crest cells (CNCCs), a transient cell population that ...generates most of the craniofacial skeleton, have much broader differentiation potential than their ectodermal lineage of origin. Here, we identify a neuroepithelial precursor population characterized by expression of canonical pluripotency transcription factors that gives rise to CNCCs and is essential for craniofacial development. Pluripotency factor
is transiently reactivated in CNCCs and is required for the subsequent formation of ectomesenchyme. Furthermore, open chromatin landscapes of Oct4
CNCC precursors resemble those of epiblast stem cells, with additional features suggestive of priming for mesenchymal programs. We propose that CNCCs expand their developmental potential through a transient reacquisition of molecular signatures of pluripotency.
The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic ...development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogeneity within the EpCAM
population of freshly isolated foetal and adult human liver identifies diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolate foetal HHyPs and confirm their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.
Cellular differentiation involves profound remodelling of chromatic landscapes, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further ...elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNA interference (RNAi) screens targeting chromatin factors during transcription-factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPS cells). Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Optimal modulation of both CAF-1 and transcription factor levels increased reprogramming efficiency by several orders of magnitude and facilitated iPS cell formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity during transcription-factor-induced cell-fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.
Hematopoietic stem cells (HSCs) self-renew and generate all blood cells. Recent studies with single cell transplants and lineage tracing suggest that adult HSCs are diverse in their reconstitution ...and lineage potentials. However, prospective isolation of these subpopulations has remained challenging. Here, we identify Neogenin-1 (NEO1) as a unique surface marker on a fraction of mouse HSCs labeled with Hoxb5, a specific reporter of long-term HSCs (LT-HSCs). We show that NEO1⁺Hoxb5⁺ LT-HSCs expand with age and respond to myeloablative stress in young mice while NEO1⁻Hoxb5⁺ LT-HSCs exhibit no significant change in number. Furthermore, NEO1⁺Hoxb5⁺ LT-HSCs are more often in the G₂/S cell cycle phase compared to NEO1⁻Hoxb5⁺ LT-HSCs in both young and old bone marrow. Upon serial transplantation, NEO1⁺Hoxb5⁺ LT-HSCs exhibit myeloid-biased differentiation and reduced reconstitution while NEO1⁻Hoxb5⁺ LT-HSCs are lineage-balanced and stably reconstitute recipients. Gene expression analysis reveals erythroid and myeloid priming in the NEO1⁺ fraction and association of quiescence and self-renewal–related transcription factors with NEO1⁻ LT-HSCs. Finally, transplanted NEO1⁺Hoxb5⁺ LT-HSCs rarely generate NEO1⁻Hoxb5⁺ LT-HSCs while NEO1⁻Hoxb5⁺ LT-HSCs repopulate both LT-HSC fractions. This supports a model in which dormant, balanced NEO1⁻Hoxb5⁺ LT-HSCs can hierarchically precede active, myeloid-biased NEO1⁺Hoxb5⁺ LT-HSCs.
LOTVS: A global collection of permanent vegetation plots Sperandii, Marta Gaia; de Bello, Francesco; Valencia, Enrique ...
Journal of vegetation science,
March/April 2022, 2022-03-00, 20220301, 2022-03, Letnik:
33, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Analysing temporal patterns in plant communities is extremely important to quantify the extent and the consequences of ecological changes, especially considering the current biodiversity crisis. ...Long‐term data collected through the regular sampling of permanent plots represent the most accurate resource to study ecological succession, analyse the stability of a community over time and understand the mechanisms driving vegetation change. We hereby present the LOng‐Term Vegetation Sampling (LOTVS) initiative, a global collection of vegetation time‐series derived from the regular monitoring of plant species in permanent plots. With 79 data sets from five continents and 7,789 vegetation time‐series monitored for at least 6 years and mostly on an annual basis, LOTVS possibly represents the largest collection of temporally fine‐grained vegetation time‐series derived from permanent plots and made accessible to the research community. As such, it has an outstanding potential to support innovative research in the fields of vegetation science, plant ecology and temporal ecology.
We present LOTVS, a global collection of vegetation time‐series derived from the regular monitoring of plant species using permanent plots. Currently including 79 data sets from five continents and 7,789 time‐series monitored for at least 6 years and mostly on an annual basis, LOTVS has the potential to support timely and innovative research in vegetation science, plant ecology and temporal ecology.
Aims
We introduce ReSurveyEurope — a new data source of resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, ...provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.
Results
ReSurveyEurope includes resurveyed vegetation plots from all habitats. Version 1.0 of ReSurveyEurope contains 283,135 observations (i.e., individual surveys of each plot) from 79,190 plots sampled in 449 independent resurvey projects. Of these, 62,139 (78%) are permanent plots, that is, marked in situ, or located with GPS, which allow for high spatial accuracy in resurvey. The remaining 17,051 (22%) plots are from studies in which plots from the initial survey could not be exactly relocated. Four data sets, which together account for 28,470 (36%) plots, provide only presence/absence information on plant species, while the remaining 50,720 (64%) plots contain abundance information (e.g., percentage cover or cover–abundance classes such as variants of the Braun‐Blanquet scale). The oldest plots were sampled in 1911 in the Swiss Alps, while most plots were sampled between 1950 and 2020.
Conclusions
ReSurveyEurope is a new resource to address a wide range of research questions on fine‐scale changes in European vegetation. The initiative is devoted to an inclusive and transparent governance and data usage approach, based on slightly adapted rules of the well‐established European Vegetation Archive (EVA). ReSurveyEurope data are ready for use, and proposals for analyses of the data set can be submitted at any time to the coordinators. Still, further data contributions are highly welcome.
We introduce ReSurveyEurope – a new data source of 79,190 resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.
We estimate DNA sequence error rates in Genbank records containing protein-coding and non-coding DNA sequences by comparing sequences of the inbred mouse strain C57BL/6J, sequenced as part of the ...mouse genome project and independently by other laboratories. C57BL/6J was produced by more than 100 generations of brother-sister mating, and can be assumed to be virtually free of residual polymorphism and mutational variation, so differences between independent sequences can be attributed to error. The estimated single nucleotide error rate for coding DNA is 0.10% (SE 0.012%), which is substantially lower than previous estimates for error rates in Genbank accessions. The estimated single nucleotide error rate for intronic DNA sequences (0.22%; SE 0.051%) is significantly higher than the rate for coding DNA. Since error rates for the mouse genome sequence are very low, the vast majority of the errors we detected are likely to be in individual Genbank accessions. The frequency of insertion-deletion (indel) errors in non-coding DNA approaches that of single nucleotide errors in non-coding DNA, whereas indel errors are uncommon in coding sequences.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
10.
Test Results of the First US ITER TF Conductor in SULTAN Martovetsky, N.N.; Hatfield, D.R.; Miller, J.R. ...
IEEE transactions on applied superconductivity,
06/2009, Letnik:
19, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
The US Domestic Agency is one of six parties supplying TF cable-in-conduit conductors (CICCs) for ITER. Previous tests have shown that measured performance of the TF CICCs can be much lower than ...expected from the strand properties at the projected uniaxial strain and that the cabling pattern may also be an important factor. Worst of all, voltage signals well below the expected critical surface could not be reliably interpreted or canceled, making test results very suspect. The TFUS1 sample was prepared to achieve multiple goals: 1) to ensure uniform current distribution and to eliminate parasitic voltage signals by improving joints, 2) to explore the potential benefits of a different cabling pattern for better support of strain-sensitive strands, and 3) to explore the source of voltage development in the cable through the use of innovative penetrating diagnostics. Test results of the first US-made samples are presented and discussed.
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