Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems
. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell ...mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.
Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for ...complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously. We built a web-based “single-cell MCA analysis” pipeline that accurately defines cell types based on single-cell digital expression. Our study demonstrates the wide applicability of the Microwell-seq technology and MCA resource.
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•Development of Microwell-seq, a high-throughput and low-cost scRNA-seq platform•Construction of a single-cell mouse cell atlas (scMCA) covering major cell types•Characterization of cellular heterogeneity with minimal batch effect•Characterization of cross-tissue cellular network at the single-cell level
Development of Microwell-seq allows construction of a mouse cell atlas at the single-cell level with a high-throughput and low-cost platform.
► Self-consistent study of the effect of 4d-dopants on the electronic structures of rutile TiO2. ► Clarification of Hubbard contribution for doped structures without gap states due to doping. ► ...Identification of potential donor (Mo, Nb) and acceptor dopants (Cd, Y) for low-cost TCOs. ► Discovery of effective gap reduction and potentially useful intermediate bands.
Electronic structures of rutile TiO2 doped with 4d transition metals were studied using the first principles method in the framework of the density functional theory. All 4d transition metal elements except for Zr were considered to substitute 1/16 of Ti lattice sites, for direct comparison of doping effect at the same level of impurity incorporation at the most stable sites, and the doping effect is expected to be positively correlated to the impurity concentration as is demonstrated through Cd-doped rutile. The results show that Y, Ag and Cd are p-type dopants, while Nb and Mo are n-type ones. These dopants also reduce the energy gap of TiO2, leading to some redshift in the optical absorption edge. Doping with Tc, Ru, Rh or Pd induces intermediate bands to divide the forbidden gap of the host phase into sub-gaps. These doping induced intermediate bands are of evident curvatures, and they are expected to act as stepping stones to relay valence electrons to the conduction band via multi-photon excitations, thus extending optical absorption of photons into the long wavelength regions of solar irradiance for enhanced photovoltaic and photo-catalytic functionalities. The effects of Hubbard U correction to the exchange–correlation functionals were also examined for some doped structures when the forbidden gap for the doped phase is from mid-gap states, while more extensive effort is expected to clarify the non-local effect associated with gap states.
Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell ...level differentiation roadmap for hPSCs has not been achieved.
We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells. Through pseudotime analysis, we construct the developmental trajectories of these progenitor cells and reveal the gene expression dynamics in the process of cell differentiation. We further reprogram primed H9 cells into naïve-like H9 cells to study the cellular-state transition process. We find that genes related to hemogenic endothelium development are enriched in naïve-like H9. Functionally, naïve-like H9 show higher potency for differentiation into hematopoietic lineages than primed cells.
Our single-cell analysis reveals the cellular-state landscape of hPSC early differentiation, offering new insights that can be harnessed for optimization of differentiation protocols.
In this article, hollow gold nanospheres (HGN) were prepared by using Co nanoparticles as sacrificial templates and varying the stoichiometric ratio of HAuCl4 over the reductants. The HGN was then ...modified on the electrode surface via a 1,6-hexanedithiol linking agent to fabricate a novel electrochemical DNA biosensor. The whole DNA biosensor fabrication process was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods with the use of ferricyanide as an electrochemical redox indicator. The probe DNA immobilization and hybridization on the modified electrode was further studied with CV and differential pulse voltammetry (DPV) methods by using Co(phen)33+ as an electrochemical hybridization indicator. Results revealed that the HGN modified electrode, especially for the HGN with the outer surface surrounded by densely spike-like nanocrystallites, could largely enhance the DNA hybridization ability. The fabricated DNA biosensor was proved to have a low detection limit (1pM) and a wide dynamic range (from 1pM to 10nM) with a high stability and reusability.
A deeper understanding of genetic regulation and functional mechanisms underlying genetic associations with complex traits and diseases is impeded by cellular heterogeneity and linkage ...disequilibrium. To address these limits, we introduce Huatuo, a framework to decode genetic variation of gene regulation at cell type and single-nucleotide resolutions by integrating deep-learning-based variant predictions with population-based association analyses. We apply Huatuo to generate a comprehensive cell type-specific genetic variation landscape across human tissues and further evaluate their potential roles in complex diseases and traits. Finally, we show that Huatuo's inferences permit prioritizations of driver cell types associated with complex traits and diseases and allow for systematic insights into the mechanisms of phenotype-causal genetic variation.
Inflammatory bowel disease (IBD), mainly categorized into Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients' ...quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation.
We conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression.
Specifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn's disease (odds ratio (OR) 95% confidence interval (CI): 0.3150.180~0.551, adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR 95% CI: 2.2851.793~2.911, adjusted P<0.001), and the volume of lateral occipital cortex in the left hemisphere demonstrated a positive relationship with Crohn's disease onset (OR 95% CI: 1.7091.671~1.747, adjusted P<0.001). In the context of reverse causality, the onset of UC or CD has led to alterations in imaging derived phenotypes associated with five disorders (anxiety, depression, schizophrenia, bipolar disorder, pain) and three functions (memory, emotion, language).
Our study has demonstrated a causal relationship between IBD and IDPs. IDPs may serve as potential biomarkers for the progression of IBD and as predictive intermediaries for the development of neurological diseases in IBD patients.
Abstract
The rapid development of high-throughput single-cell RNA sequencing technology offers a good opportunity to dissect cell heterogeneity of animals. A large number of organism-wide single-cell ...atlases have been constructed for vertebrates such as
Homo sapiens
,
Macaca fascicularis
,
Mus musculus
and
Danio rerio
. However, an intermediate taxon that links mammals to vertebrates of more ancient origin is still lacking. Here, we construct the first
Xenopus
cell landscape to date, including larval and adult organs. Common cell lineage-specific transcription factors have been identified in vertebrates, including fish, amphibians and mammals. The comparison of larval and adult erythrocytes identifies stage-specific hemoglobin subtypes, as well as a common type of cluster containing both larval and adult hemoglobin, mainly at NF59. In addition, cell lineages originating from all three layers exhibits both antigen processing and presentation during metamorphosis, indicating a common regulatory mechanism during metamorphosis. Overall, our study provides a large-scale resource for research on
Xenopus
metamorphosis and adult organs.
Dear Editor, Embryonic stem cell （ES cell） lines were first generated by culturing mouse inner cell mass （ICM） on feeder layers in 1981 1. However, in large domestic animals, attempts to establish ES ...cell lines from ICM of blastocysts or the later epiblast have not been successful.
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