| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Gao, R, et al.
(författare)
-
Resetting histone modifications during human prenatal germline development
- 2023
-
Ingår i: Cell discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 9:1, s. 14-
-
Tidskriftsartikel (refereegranskat)abstract
- Histone modifications play critical roles in regulating gene expression and present dynamic changes during early embryo development. However, how they are reprogrammed during human prenatal germline development has not yet been elucidated. Here, we map the genome-wide profiles of three key histone modifications in human primordial germ cells (hPGCs) from weeks 8 to 23 of gestation for the first time by performing ULI-NChIP-seq. Notably, H3K4me3 exhibits a canonical promoter-enriched pattern, though with relatively lower enrichment, and is positively correlated with gene expression in globally hypomethylated hPGCs. In addition, H3K27me3 presents very low enrichment but plays an important role in not only dynamically governing specific bivalent promoters but also impeding complete X chromosome reactivation in female hPGCs. Given the activation effects of both global DNA demethylation and H3K4me3 signals, repressive H3K9me3 and H3K27me3 marks are jointly responsible for the paradoxical regulation of demethylation-resistant regions in hPGCs. Collectively, our results provide a unique roadmap of three core histone modifications during hPGC development, which helps to elucidate the architecture of germ cell reprogramming in an extremely hypomethylated DNA environment.
|
|
| 7. |
- Gao, X, et al.
(författare)
-
Longitudinal patient-reported outcomes 1 year after thoracoscopic segmentectomy versus lobectomy for early-stage lung cancer: a multicentre, prospective cohort study protocol
- 2023
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:1, s. e067841-
-
Tidskriftsartikel (refereegranskat)abstract
- Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes—such as symptoms, daily functioning and quality of life—between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery.Methods and analysisOverall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery—a validated lung cancer surgery-specific scale—will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients’ quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student’s t-test, non-parametric test or Χ2test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups.Ethics and disseminationThe Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals.Trial registration numberChiCTR2200060753.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Mei, J, et al.
(författare)
-
Development and external validation of a COVID-19 mortality risk prediction algorithm: a multicentre retrospective cohort study
- 2020
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:12, s. e044028-
-
Tidskriftsartikel (refereegranskat)abstract
- This study aimed to develop and externally validate a COVID-19 mortality risk prediction algorithm.DesignRetrospective cohort study.SettingFive designated tertiary hospitals for COVID-19 in Hubei province, China.ParticipantsWe routinely collected medical data of 1364 confirmed adult patients with COVID-19 between 8 January and 19 March 2020. Among them, 1088 patients from two designated hospitals in Wuhan were used to develop the prognostic model, and 276 patients from three hospitals outside Wuhan were used for external validation. All patients were followed up for a maximal of 60 days after the diagnosis of COVID-19.MethodsThe model discrimination was assessed by the area under the receiver operating characteristic curve (AUC) and Somers’ D test, and calibration was examined by the calibration plot. Decision curve analysis was conducted.Main outcome measuresThe primary outcome was all-cause mortality within 60 days after the diagnosis of COVID-19.ResultsThe full model included seven predictors of age, respiratory failure, white cell count, lymphocytes, platelets, D-dimer and lactate dehydrogenase. The simple model contained five indicators of age, respiratory failure, coronary heart disease, renal failure and heart failure. After cross-validation, the AUC statistics based on derivation cohort were 0.96 (95% CI, 0.96 to 0.97) for the full model and 0.92 (95% CI, 0.89 to 0.95) for the simple model. The AUC statistics based on the external validation cohort were 0.97 (95% CI, 0.96 to 0.98) for the full model and 0.88 (95% CI, 0.80 to 0.96) for the simple model. Good calibration accuracy of these two models was found in the derivation and validation cohort.ConclusionThe prediction models showed good model performance in identifying patients with COVID-19 with a high risk of death in 60 days. It may be useful for acute risk classification.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Chen, G, et al.
(författare)
-
Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
- 2016
-
Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 26:10, s. 1342-1354
-
Tidskriftsartikel (refereegranskat)abstract
- Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Ma, Q, et al.
(författare)
-
ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4142-
-
Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-β cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-β cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-β cells that are useful as a potential source for cell replacement therapies.
|
|
| 21. |
- Nichterwitz, S, et al.
(författare)
-
Laser capture microscopy coupled with Smart-seq2 for precise spatial transcriptomic profiling
- 2016
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 12139-
-
Tidskriftsartikel (refereegranskat)abstract
- Laser capture microscopy (LCM) coupled with global transcriptome profiling could enable precise analyses of cell populations without the need for tissue dissociation, but has so far required relatively large numbers of cells. Here we report a robust and highly efficient strategy for LCM coupled with full-length mRNA-sequencing (LCM-seq) developed for single-cell transcriptomics. Fixed cells are subjected to direct lysis without RNA extraction, which both simplifies the experimental procedures as well as lowers technical noise. We apply LCM-seq on neurons isolated from mouse tissues, human post-mortem tissues, and illustrate its utility down to single captured cells. Importantly, we demonstrate that LCM-seq can provide biological insight on highly similar neuronal populations, including motor neurons isolated from different levels of the mouse spinal cord, as well as human midbrain dopamine neurons of the substantia nigra compacta and the ventral tegmental area.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Topuz, G, et al.
(författare)
-
Origin and significance of Early Miocene high‑potassium I-type granite plutonism in the East Anatolian plateau (the Taşlıçay intrusion)
- 2019
-
Ingår i: Lithos. - : Elsevier BV. - 0024-4937. ; 348-349
-
Tidskriftsartikel (refereegranskat)abstract
- © 2019 Elsevier B.V. The Early Miocene high-K I-type plutonic rocks constitute the early products of the Neogene to Quaternary magmatism, and the youngest exposed intrusions in the East Anatolian plateau. Here we deal with the petrogenesis of the Early Miocene Taşlıçay intrusion covering an area of ∼62 km2. The intrusion comprises leucogranite, and minor gabbro-monzodiorite and rhyolite porphyry. U-Pb dating of zircons from the leucogranite, monzodiorite and rhyolite porphyry yielded identical igneous crystallization ages of ∼19 Ma (Early Miocene). According to the modified alkali-lime index, the leucogranite and the rhyolite porphyry are alkali-calcic, while the gabbro-monzodiorite is transitional calcic to calc-alkalic. On variation diagrams, the gabbro-monzodiorite and the leucogranite as well as rhyolite porphyry form distinct bimodal groupings, whereby the leucogranite display well-defined linear differentiation trends, in contrast to the gabbro-monzodiorite. The leucogranite has relatively fractionated rate earth element (REE) patterns with concave-upward shapes and significant negative Eu anomalies; middle REEs are hardly fractionated with respect to heavy REEs. The gabbro-monzodiorite is characterized by high abundances of incompatible elements, slightly fractionated chondrite-normalized REE patterns with feebly negative Eu anomaly. The rhyolite porphyry is compositionally similar to the leucogranite. The geochemical features imply a fractionating mineral assemblage of hornblende, plagioclase and biotite for the leucogranite, and hornblende and ± plagioclase for the gabbro-monzodiorite. All the rock types display a narrow Sr and Nd isotopic variation (initial 87Sr/86Sr = 0.7053 to 0.7065; initial εNd = −0.5 to −3.8). The leucogranite and rhyolite porphyry exhibit gradually slightly higher initial 87Sr/86Sr and lower initial 143Nd/ 144Nd ratios relative to the gabbro-monzodiorite. Similarly, δ18O and initial εHf values of zircons suggest slightly increasing amount of crustal component from the leucogranite to the rhyolite porphyry. The gabbro-monzodiorite is probably related to partial melts from the slightly enriched lithospheric mantle. The magmas of the leucogranite and the rhyolite porphyry, on the other hand, probably resulted from the remelting of a middle- to high-K basic to intermediate rocks, compositionally similar to the gabbro-monzodiorite, and assimilated gradually slightly increasing amount of old high-silica crustal material. Several lines of evidence such as (i) presence of the well-developed dike swarm of rhyolite porphyry at the north eastern margin of the intrusion, (ii) exhumation of the intrusion at the earth's surface by Middle Miocene, (iii) widespread apatite fission tract ages between 22 and 16 Ma from literature, and (iv) the absence of the exposed intrusions younger than the Early Miocene suggest that the Early Miocene represents probably a time of continental extension and exhumation in Eastern Anatolia and NW Iran.
|
|
| 25. |
|
|
