Technical Advances in Single-Cell RNA Sequencing and Applications in Normal and Malignant Hematopoiesis

Single-cell RNA sequencing (scRNA-seq) has been tremendously developed in the past decade owing to overcoming challenges associated with isolation of massive quantities of single cells. Previously, cell heterogeneity and low quantities of available biological material posed significant difficulties to scRNA-seq. Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of normal and malignant hematopoietic cells; this heterogeneity has often been ignored in omics studies. The application of scRNA-seq has profoundly changed our comprehension of many biological phenomena, including organ development and carcinogenesis. Hematopoiesis, is actually a maturation process for more than ten distinct blood and immune cells, and is thought to be critically involved in hematological homeostasis and in sustaining the physiological functions. However, aberrant hematopoiesis directly leads to hematological malignancy, and a deeper understanding of malignant hematopoiesis will provide deeper insights into diagnosis and prognosis for patients with hematological malignancies. Here, we aim to review the recent technical progress and future prospects for scRNA-seq, as applied in physiological and malignant hematopoiesis, in efforts to further understand the hematopoietic hierarchy and to illuminate personalized therapy and precision medicine approaches used in the clinical treatment of hematological malignancies

Establishment and characterization of immortalized human eutopic endometrial stromal cells.

PROBLEM(#br)The application of primary eutopic endometrial cells from endometriosis patients in research is restricted for short life span, dedifferentiation of hormone responsiveness.(#br)METHOD OF STUDY(#br)Human telomerase reverse transcriptase (hTERT)-induced immortalized cells (iheESCs) were infected by lentivirus. mRNA level was examined by qRT-PCR, and protein expression was quantified by Western blot. CCK-8 and EdU assay were assigned to assess the proliferation. The migration and invasion of cells were assessed by transwell assay. Clone formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities.(#br)RESULTS(#br)hTERT mRNA and protein were significantly expressed higher in iheESCs compared to primary cells. iheESCs grew without morphological change for 42 passages which is much longer than 18 passages of primary cells. There was no obvious difference between primary cells and iheESCs in growth, mobility, and chromosome karyotype. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and estrogen/progesterone receptors remained unchanged. The decidualization of iheESCs could be induced by progesterone and cAMP. Estrogen increased the proliferation and mobility of iheESCs, and lipopolysaccharides (LPS) induced the IL-1β and IL-6 promoting inflammatory response. The colony-forming ability of iheESCs, like primary cells, was lower than Ishikawa cells. In addition, tumorigenicity assay indicated that iheESCs were unable to trigger tumor formation in BALB/c nude mouse.(#br)CONCLUSIONS(#br)This study established and characterized iheESCs that kept the cellular physiology of primary cells and were not available with tumorigenic ability. Thus, iheESCs would be useful as in vitro cell model to investigate pathogenesis of endometriosis

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC

Late-life depression: Epidemiology, phenotype, pathogenesis and treatment before and during the COVID-19 pandemic

Late-life depression (LLD) is one of the most common mental disorders among the older adults. Population aging, social stress, and the COVID-19 pandemic have significantly affected the emotional health of older adults, resulting in a worldwide prevalence of LLD. The clinical phenotypes between LLD and adult depression differ in terms of symptoms, comorbid physical diseases, and coexisting cognitive impairments. Many pathological factors such as the imbalance of neurotransmitters, a decrease in neurotrophic factors, an increase in β-amyloid production, dysregulation of the hypothalamic-pituitary-adrenal axis, and changes in the gut microbiota, are allegedly associated with the onset of LLD. However, the exact pathogenic mechanism underlying LLD remains unclear. Traditional selective serotonin reuptake inhibitor therapy results in poor responsiveness and side effects during LLD treatment. Neuromodulation therapies and complementary and integrative therapies have been proven safe and effective for the treatment of LLD. Importantly, during the COVID-19 pandemic, modern digital health intervention technologies, including socially assistive robots and app-based interventions, have proven to be advantageous in providing personal services to patients with LLD

Manipulating spatial structure of high-order quantum coherence with entangled photons

High-order quantum coherence reveals the statistical correlation of quantum particles. Manipulation of quantum coherence of light in temporal domain enables to produce single-photon source, which has become one of the most important quantum resources. High-order quantum coherence in spatial domain plays a crucial role in a variety of applications, such as quantum imaging, holography and microscopy. However, the active control of high-order spatial quantum coherence remains a challenging task. Here we predict theoretically and demonstrate experimentally the first active manipulation of high-order spatial quantum coherence by mapping the entanglement of spatially structured photons. Our results not only enable to inject new strength into current applications, but also provide new possibilities towards more wide applications of high-order quantum coherence.Comment: 11 pages, 5 figure

Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase

This work was supported by: National Natural Science Foundation of China http://www.nsfc.gov.cn/; #81620108021: Fetal Brain Maldevelopment Caused by Sox2 Downregulation during Congenital Cytomegalovirus Infection; #31600145: The mechanism of HCMV-IE1 regulating Hes1 expression and rhythm in neural progenitor cells; #81571355: Construction of Murine Cytomegalovirus Derived viral tools for Specific Glia Tracing; #81271850: The regulation mechanism of HCMV infection on Notch signaling pathway in NPCs; and Sino-Africa Joint Research Center, Chinese Academy of Sciences http://www.sinafrica.cas.cn/; #SAJC201605: Geographical distribution and genetic variation of pathogens in Africa. This work is tightly linked to or is an important component of the above list projects, and is financially supported by all the fundings.Congenital human cytomegalovirus (HCMV) infection is the leading cause of neurological disabilities in children worldwide, but the mechanisms underlying these disorders are far from well-defined. HCMV infection has been shown to dysregulate the Notch signaling pathway in human neural progenitor cells (NPCs). As an important downstream effector of Notch signaling, the transcriptional regulator Hairy and Enhancer of Split 1 (Hes1) is essential for governing NPC fate and fetal brain development. In the present study, we report that HCMV infection downregulates Hes1 protein levels in infected NPCs. The HCMV 72-kDa immediate-early 1 protein (IE1) is involved in Hes1 degradation by assembling a ubiquitination complex and promoting Hes1 ubiquitination as a potential E3 ubiquitin ligase, followed by proteasomal degradation of Hes1. Sp100A, an important component of PML nuclear bodies, is identified to be another target of IE1-mediated ubiquitination. A C-terminal acidic region in IE1, spanning amino acids 451 to 475, is required for IE1/Hes1 physical interaction and IE1-mediated Hes1 ubiquitination, but is dispensable for IE1/Sp100A interaction and ubiquitination. Our study suggests a novel mechanism linking downregulation of Hes1 protein to neurodevelopmental disorders caused by HCMV infection. Our findings also complement the current knowledge of herpesviruses by identifying IE1 as the first potential HCMV-encoded E3 ubiquitin ligase.Publisher PDFPeer reviewe

A Comprehensive Study of Gamma-Ray Burst Optical Emission: I. Flares and Early Shallow Decay Component

Well-sampled optical lightcurves of 146 gamma-ray bursts (GRBs) are compiled from the literature. By empirical fitting we identify eight possible emission components and summarize the results in a "synthetic" lightcurve. Both optical flare and early shallow-decay components are likely related to long-term central engine activities. We focus on their statistical properties in this paper. Twenty-four optical flares are obtained from 19 GRBs. The isotropic R-band energy is smaller than 1% of $E_{\gamma, \rm iso}$. The relation between isotropic luminosities of the flares and gamma-rays follows $L^{\rm F}_{\rm R, iso}\propto L_{{\gamma}, \rm iso}^{1.11\pm 0.27}$. Later flares tend to be wider and dimmer, i.e., $w^{\rm F}\sim t^{\rm F}_{\rm p}/2$ and $L^{\rm F}_{\rm R, iso}\propto [t^{\rm F}_{\rm p}/(1+z)]^{-1.15\pm0.15}$. The detection probability of the optical flares is much smaller than that of X-ray flares. An optical shallow decay segment is observed in 39 GRBs. The relation between the break time and break luminosity is a power-law, with an index of $-0.78\pm 0.08$, similar to that derived from X-ray flares. The X-ray and optical breaks are usually chromatic, but a tentative correlation is found. We suggest that similar to the prompt optical emission that tracks $\gamma$-rays, the optical flares are also related to the erratic behavior of the central engine. The shallow decay component is likely related to a long-lasting spinning-down central engine or piling up of flare materials onto the blastwave. Mixing of different emission components may be the reason of the diverse chromatic afterglow behaviors.Comment: 43 pages, 13 figures, 3 tables, accepted for publication in Ap

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies

BackgroundDepression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression.MethodElectronic databases were searched using the search terms “depression,” “emotion recognition,” and “neuroimaging” from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis.ResultsWe retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001).ConclusionAmong depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution.Systematic review registrationhttps://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057

Constraining GRB Initial Lorentz Factor with the Afterglow Onset Feature and Discovery of a Tight Gamma_0-E_iso Correlation

The onset of GRB afterglow is characterized by a smooth bump in the early afterglow lightcurve. We make an extensive search for such a feature. Twenty optically selected GRBs and 12 X-ray selected GRBs are found, among which 17 optically selected GRBs and 2 X-ray-selected GRBs have redshift measurements. We fit the lightcurves with a smooth broken power-law and measure the temporal characteristic timescales of the bumps at FWHM. Strong mutual correlations among these timescales are found, and a dimmer and broader bump tends to peak at a later peak time. The ratio of rising to decaying timescales is almost universal among bursts, but the ratio of the rising time to the peak time varies from 0.3~1. The E_iso is tightly correlated with the peak luminosity and the peak time of the bump in the burst frame. Assuming that the bumps signal the deceleration of the GRB fireballs in a constant density medium, we calculate the initial Lorentz factor (Gamma_0) and the deceleration radius (R_dec) of the GRBs in the optical-selected sample. It is found that Gamma_0 are typically a few hundreds, and the typical deceleration radius is R_dec~10^{17} cm. More intriguingly, a tight correlation between the Gamma_0 and E_iso is found, namely Gamma_0 ~ 195 E_iso, 52}^{0.27} (satisfied for both the optical and X-ray z-known samples). It is helpful to understand GRB physics, and may serve as an indicator of Gamma_0. We find that the early bright X-rays are usually dominated by a different component from the external shock emission, but occasionally (for one case) an achromatic deceleration feature is observed. Components in X-rays would contribute to the diversity of the observed X-ray lightcurves (abridge).Comment: 15 pages, including 4 tables and 7 figures, Submitted to Ap