KLF1和KLF9对K562细胞红系分化的协同调控作用

Krüppel样因子(Krüppel-like factors,KLFs)是锌指蛋白超家族的一个亚家族,参与细胞内的多种生理、病理过程,该家族成员在红细胞分化发育过程中发挥非常重要的作用,但是家族成员间对红系分化的协同调控作用还鲜有报道。本课题组前期研究发现,KIF家族成员KLF1和KLF9在已分化的红系细胞中的表达水平显著高于造血干细胞。为进一步探讨二者在红系分化中是否存在协同作用,本研究在K562细胞中分别过表达/敲低表达KLF1和KLF9,检测二者表达的相关性,发现KLF1和KLF9的基因表达呈现正相关,且二者共表达可以显著促进K562细胞红系分化,特异地增强β-珠蛋白的表达。通过对KLF1、KLF9单独和共同过表达、敲低表达的K562细胞转录组数据的分析发现二者可能通过PI3K-Akt和FoxO通路协同调控红系分化,FOS、TF、IL8是协同调控的候选靶基因。本研究结果为后续深入研究KLF1和KLF9协同调控红系分化的分子机制奠定了基础。

The main chemical constituents from Piper amalago: A review of its phytochemistry

Piper amalago(P.amalago)is a traditional medicine in Brazil for the treatment of leishmanial.Owing to its rare occurrence and potent pharmacological activities,efforts have been devoted to the identification of its diverse constituents,especially terpenoids.Researchers have found that the major constituents of P.amalago were amides,monoterpenes,norisoprenoids,sesquiterpenes,aliphatic hydrocarbons and aromatic hydrocarbons.The amides show anxiolytic,anti-inflammatory,antileishmanial and antinociceptive activity.This review summarizes the research progress of the structural diversity and pharmacological activities of P.amalago.

Global transcriptome analysis for identification of interactions between coding and noncoding RNAs during human erythroid differentiation

Studies on coding genes, miRNAs, and lncRNAs during erythroid development have been performed in recent years. However, analysis focusing on the integration of the three RNA types has yet to be done. In the present study, we compared the dynamics of coding genes, miRNA, and IncRNA expression profiles. To explore dynamic changes in erythropoiesis and potential mechanisms that control these changes in the transcriptome level, we took advantage of high throughput sequencing technologies to obtain transcriptome data from cord blood hematopoietic stem cells and the following four erythroid differentiation stages, as well as from mature red blood cells. Results indicated that lncRNAs were promising cell marker candidates for erythroid differentiation. Clustering analysis classified the differentially expressed genes into four subtypes that corresponded to dynamic changes during sternness maintenance, mid-differentiation, and maturation. Integrated analysis revealed that noncoding RNAs potentially participated in controlling blood cell maturation, and especially associated with heine metabolism and responses to oxygen species and DNA damage. These regulatory interactions were displayed in a comprehensive network, thereby inferring correlations between RNAs and their associated functions. These data provided a substantial resource for the study of normal erythropoiesis, which will permit further investigation and understanding of erythroid development and acquired erythroid disorders.

Mapping Human Pluripotent Stem Cell-derived Erythroid Differentiation by Single-cell Transcriptome Analysis

There is an imbalance between the supply and demand of functional red blood cells(RBCs)in clinical applications.This imbalance can be addressed by regenerating RBCs using several in vitro methods.Induced pluripotent stem cells(iPSCs)can handle the low supply of cord blood and the ethical issues in embryonic stem cell research,and provide a promising strategy to eliminate immune rejection.However,no complete single-cell level differentiation pathway exists for the iPSC-derived erythroid differentiation system.In this study,we used iPSC line BC1 to establish a RBC regeneration system.The 10X Genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectory on day 14 of the regeneration system.We observed that iPSC differentiation was not synchronized during embryoid body(EB)culture.The cells(on day 14)mainly consisted of mesodermal and various blood cells,similar to the yolk sac hematopoiesis.We identified six cell classifications and characterized the regulatory transcription factor(TF)networks and cell-cell contacts underlying the system.iPSCs undergo two transformations during the differentiation trajectory,accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes.We identified erythroid cells at different stages,such as burst-forming unit erythroid(BFU-E)and orthochromatic erythroblast(ortho-E)cells,and found that the regulation of TFs(e.g.,TFDP1 and FOXO3)is erythroid-stage specific.Immune erythroid cells were identified in our system.This study provides systematic theoretical guidance for optimizing the iPSC-derived erythroid differentiation system,and this system is a useful model for simulating in vivo hematopoietic development and differentiation.

3D X-ray microscopy with a CsPbBr3 nanowire scintillator

X-ray microscopy is an essential imaging method in many scientific fields,which can be extended to three-dimensional(3D)using tomography.Recently,metal halide perovskite(MHP)nanomaterials have become a promising candidate for X-ray scintillators,due to their high light yield,high spatial resolution,and easy fabrication.Tomography requires many projections and therefore scintillators with excellent stability.This is challenging for MHPs,which often suffer from fast degradation under X-ray irradiation and ambient conditions.Here,we demonstrate that MHP scintillators of CsPbBr3 nanowires(diameter:60 nm,length:5–9μm)grown in anodized aluminum oxide(CsPbBr3 NW/AAO)have sufficient stability for X-ray micro-tomography.A tomogram was taken with a Cu X-ray source over 41 h(dose 4.2 Gyair).During this period the scintillator brightness fluctuated less than 5%,which enabled a successful reconstruction.A long-term study with 2 weeks of continuous X-ray exposure(37.5 Gyair)showed less than 14%fluctuations in brightness and no long-term degradation,despite variations in the ambient relative humidity from 7.4%RH to 34.2%RH.The resolution was stable at(180±20)lp·mm−1,i.e.,about 2.8 micron.This demonstrates that CsPbBr3 NW/AAO scintillators are promising candidates for high resolution X-ray imaging detectors.

Transcriptome Analysis of Monozygotic Twin Brothers with Childhood Primary Myelofibrosis

Primary myelofibrosis （PMF） is a chronic myeloproliferative disorder in human bone marrow. Over 50% of patients with myelofibrosis have mutations in JAK2, MPL, or CALR. However, these mutations are rarely detected in children, suggesting a difference in the pathogenesis of childhood PMF. In this study, we investigated the response to drug treatment of a monozygotic twin pair with typical childhood PMF. The twin exhibited different clinical outcomes despite following

Long noncoding RNA PCED1B-AS1 promotes erythroid differentiation coordinating with GATA1 and chromatin remodeling

Erythropoiesis is a complex and sophisticated multi-stage process regulated by a variety of factors,including the transcription factor GATA1 and non-coding RNA.GATA1 is regarded as an essential transcriptional regulator promoting transcription of erythroidspecific genes—such as long non-coding RNAs(lncRNA).Here,we comprehensively screened lncRNAs that were potentially regulated by GATA1 in erythroid cells.We identified a novel lncRNA—PCED1B-AS1—and verified its role in promoting erythroid differentiation of K562 erythroid cells.We also predicted a model in which PCED1B-AS1 participates in erythroid differentiation via dynamic chromatin remodeling involving GATA1.The relationship between lncRNA and chromatin in the process of erythroid differentiation remains to be revealed,and in our study we have carried out preliminary explorations.

Deconstructing Vibrational Motions on the Potential Energy Surfaces of Hydrogen-Bonded Complexes

Internal vibrations underlie transient structure formation,spectroscopy,and dynamics.However,at least two challenges exist when aiming to elucidate the contributions of vibrational motions on the potential energy surfaces.One is the acquisition of well-resolved experimental infrared spectra,and the other is the development of efficient theoretical methodologies that reliably predict band positions,relative intensities,and substructures.Here,we report size-specific infrared spectra of ammonia clusters to address these two challenges.Unprecedented agreement between experiment and state-of-the-art quantum simulations reveals that the vibrational spectra are mainly contributed by proton-donor ammonia.A striking Fermi resonance observed at approximately 3210 and 3250 cm^(−1)originates from the coupling of NH symmetric stretch fundamentals with overtones of free and hydrogen-bonded NH bending,respectively.These novel,intriguing findings contribute to a better understanding of vibrational motions in a large variety of hydrogen-bonded complexes with orders of magnitude improvements in spectral resolution,efficiency,and specificity.