The distribution and abundance of immune cells, particularly T‐cell subsets, play pivotal roles in cancer immunology and therapy. T cells have many subsets with specific function and current methods ...are limited in estimating them, thus, a method for predicting comprehensive T‐cell subsets is urgently needed in cancer immunology research. Here, Immune Cell Abundance Identifier (ImmuCellAI), a gene set signature‐based method, is introduced for precisely estimating the abundance of 24 immune cell types including 18 T‐cell subsets, from gene expression data. Performance evaluation on both the sequencing data with flow cytometry results and public expression data indicate that ImmuCellAI can estimate the abundance of immune cells with superior accuracy to other methods especially on many T‐cell subsets. Application of ImmuCellAI to immunotherapy datasets reveals that the abundance of dendritic cells, cytotoxic T, and gamma delta T cells is significantly higher both in comparisons of on‐treatment versus pre‐treatment and responders versus non‐responders. Meanwhile, an ImmuCellAI result‐based model is built for predicting the immunotherapy response with high accuracy (area under curve 0.80–0.91). These results demonstrate the powerful and unique function of ImmuCellAI in tumor immune infiltration estimation and immunotherapy response prediction.
Immune Cell Abundance Identifier (ImmuCellAI) is a gene set signature‐based method for precisely estimating the abundance of 24 immune cell types including 18 T‐cell subsets. Application of ImmuCellAI to immunotherapy datasets reveals the dynamic change of immune cell abundance. An ImmuCellAI result‐based model for predicting the immunotherapy response achieves high accuracy with area under curve 0.80–0.91.
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.
Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological ...insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.
Transcription factors (TFs) as key regulators play crucial roles in biological processes. The identification of TF–target regulatory relationships is a key step for revealing functions of TFs and ...their regulations on gene expression. The accumulated data of chromatin immunoprecipitation sequencing (ChIP-seq) provide great opportunities to discover the TF–target regulations across different conditions. In this study, we constructed a database named hTFtarget, which integrated huge human TF target resources (7190 ChIP-seq samples of 659 TFs and high-confidence binding sites of 699 TFs) and epigenetic modification information to predict accurate TF–target regulations. hTFtarget offers the following functions for users to explore TF–target regulations: (1) browse or search general targets of a query TF across datasets; (2) browse TF–target regulations for a query TF in a specific dataset or tissue; (3) search potential TFs for a given target gene or non-coding RNA; (4) investigate co-association between TFs in cell lines; (5) explore potential co-regulations for given target genes or TFs; (6) predict candidate TF binding sites on given DNA sequences; (7) visualize ChIP-seq peaks for different TFs and conditions in a genome browser. hTFtarget provides a comprehensive, reliable and user-friendly resource for exploring human TF–target regulations, which will be very useful for a wide range of users in the TF and gene expression regulation community. hTFtarget is available at http://bioinfo.life.hust.edu.cn/hTFtarget.
Ferroptosis is a newly identified form of nonapoptotic regulated cell death characterized by iron-dependent accumulation of lipid reactive oxygen species. Morphologically and biochemically different ...from known types of cell death and apoptosis, ferroptosis promotes nervous system diseases, renal failure, ischemia-reperfusion injury, and the treatment of tumors. It could be induced by several mechanisms, including inhibition of glutathione peroxidase 4, lack of cysteine, and peroxidation of polyunsaturated fatty acids, but could be inhibited by iron chelators, lipophilic antioxidants, and some specific inhibitors. Ferroptosis is found to be closely related to the tumorigenesis, invasion, and metastasis of tumors. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), microRNAs, and circular RNAs, do not encode proteins. NcRNAs are found to be capable of regulating the molecular mechanism of ferroptosis in tumor cells post transcription. Ferroptosis provides a new method for cancer treatment. Although several studies have confirmed the important role of ferroptosis in cancer treatment, its specific affecting mechanism is unclear. Here we reviewed the molecular mechanism of ferroptosis in tumor cells and the relationship between ferroptosis and the three important ncRNAs.
LSD1 (KDM1A) is a histone demethylase that plays both oncogenic and tumor suppressor roles in breast cancer. However, the exact contexts under which it plays these opposite functions remain largely ...elusive. By characterizing its role in luminal breast epithelial cells, here we show that inhibition of LSD1 by both genetic and pharmacological approaches increases their invasion and migration, whereas its inhibition by genetic approach, but not by pharmacological approach, impairs their proliferation/survival. Induced loss of LSD1 in luminal cells in a mouse model of luminal breast cancer, MMTV-PyMT, leads to a profound increase in lung metastasis. Mechanistically, LSD1 interacts with GATA3, a key luminal-specific transcription factor (TF), and their common target genes are highly related to breast cancer. LSD1 positively regulates GATA3 expression. It also represses expression of TRIM37, a breast epithelial oncogene encoding a histone H2A ubiquitin ligase, and ELF5, a key TF gene for luminal progenitors and alveolar luminal cells. LSD1-loss also leads to reduced expression of several cell-cell adhesion genes (e.g., CDH1, VCL, CTNNA1), possibly via TRIM37-upregulation and subsequently TRIM37-mediated repression. Collectively, our data suggest LSD1 largely plays a tumor suppressor role in luminal breast cancer and the oncogenic program associated with LSD1-inhibition may be suppressed via TRIM37-inhibition.
Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well ...understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.
Summary
Bioactive triterpenes feature complex fused‐ring structures, primarily shaped by the first‐committed enzyme, 2,3‐oxidosqualene cyclases (OSCs) in plant triterpene biosynthesis. Triterpenes ...with B,C‐ring‐opened skeletons are extremely rare with unknown formation mechanisms, harbouring unchartered chemistry and biology.
Here, through mining the genome of Chenopodium quinoa followed by functional characterization, we identified a stress‐responsive and neofunctionalized OSC capable of generating B,C‐ring‐opened triterpenes, including camelliol A and B and the novel (−)‐quinoxide A as wax components of the specialized epidermal bladder cells, namely the quinoxide synthase (CqQS).
Protein structure analysis followed by site‐directed mutagenesis identified key variable amino acid sites underlying functional interconversion between pentacyclic β‐amyrin synthase (CqbAS1) and B,C‐ring‐opened triterpene synthase CqQS. Mutation of one key residue (N612K) in even evolutionarily distant Arabidopsis β‐amyrin synthase could generate quinoxides, indicating a conserved mechanism for B,C‐ring‐opened triterpene formation in plants. Quantum computation combined with docking experiments further suggests that conformations of conserved W613 and F413 of CqQS might be key to selectively stabilizing intermediate carbocations towards B,C‐ring‐opened triterpene formation.
Our findings shed light on quinoa triterpene skeletal diversity and mechanisms underlying B,C‐ring‐opened triterpene biosynthesis, opening avenues towards accessing their chemistry and biology and paving the way for quinoa trait engineering and quality improvement.
The development of low-cost bifunctional electrocatalysts with both a high activity and long durability is critical for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). The ...reasonable design and construction of bifunctional electrocatalysts is the key to energy storage and energy conversion technologies. In this study, transition metal carbon nitrides were used as a substitute for the precious metal catalyst, the Ni-Co-BTC (metal organic framework (MOF)) mixed with polyacrylonitrile (PAN) using electrostatic spinning technology to prepare the bamboo-like nanofibers precursor (Ni-Co-BTC@PAN). A series of electrocatalytic materials (NiCo-X@N-CNFs-
T
s,
T
= 700, 800, 900 °C) were synthesized with nitrogen-doped carbon nanofibers coated with NiCo alloy nanoparticles using high temperature carbonization at different temperatures. We studied the effects of different calcination temperatures and different Ni/Co molar ratios of NiCo-X@N-CNFs-
T
s (
T
= 700, 800, 900 °C) on the bifunctional catalytic performance of the ORR/OER. The composite, NiCo-0.8@N-CNFs-800, exhibited a highly doped-N level, uniform NiCo alloy nanoparticle dispersion and decentralized NiCo-N
x
active sites, therefore affording an excellent bifunctional electrocatalytic performance. The ORR onset potential on NiCo-0.8@N-CNFs-800 was 0.91 V and the half-wave potential (
E
1/2
) was 0.82 V, the NiCo-0.8@N-CNFs-800 corresponded to the minimum potential of 1.61 V at the current density of 10 mA cm
−2
among all of the NiCo-X@N-CNFs-
T
s hybrids under the OER condition. The NiCo-0.8@N-CNFs-800 catalyst exhibited a low reversible overpotential of 0.79 V between the ORR (
E
1/2
) and OER (
E
j
= 10 mA cm
−2
) with excellent stability, durability and methanol tolerance, even surprisingly superior to the commercial Pt/C and RuO
2
catalysts. This work provides a general strategy and useful guidance for the design and development of a variety of multifunctional non-noble metal catalysts for energy applications.
Bamboo-like nanofibers NiCo-0.8@N-CNFs-800 demonstrated an excellent bifunctional electrocatalytic performance, with a low reversible overpotential of 0.79 V between the ORR (
E
1/2
) and OER (
E
j
= 10 mA cm
−2
).
Two extremely halophilic strains, designated SYSU A558-1
T
and SYSU A121-1, were isolated from a saline sediment sample collected from Aiding salt-lake, China. Cells of strains SYSU A558-1
T
and SYSU ...A121-1 were Gram-stain-negative, coccoid, and non-motile. The strains were aerobic and grew at NaCl concentration of 10–30% (optimum, 20–22%), at 20–55 °C (optimum, 37–42 °C) and at pH 6.5–8.5 (optimum, 7.0–8.0). Cells lysed in distilled water. The polar lipids were phosphatidyl choline, phosphatidylglycerol phosphate methyl ester, disulfated diglycosyl diether-1 and unidentified glycolipid. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the two strains SYSU A558-1
T
and SYSU A121-1 were closely related to the membranes of the genus
Haloterrigena.
Phylogenetic and phylogenomic trees of strains SYSU A558-1
T
and SYSU A121-1 demonstrated a robust clade with
Haloterrigena turkmenica, Haloterrigena salifodinae
and
Haloterrigena salina
. The genomic DNA G + C content of strains SYSU A558-1
T
and SYSU A121-1 were 65.8 and 65.0%, respectively. Phenotypic, phylogenetic, chemotaxonomic and genome analysis suggested that the two strains SYSU A558-1
T
and SYSU A121-1 represent a novel species of the genus
Haloterrigena
, for which the name
Haloterrigena gelatinilytica
sp. nov. is proposed. The type strain is SYSU A558-1
T
(= KCTC 4259
T
= CGMCC 1.15953
T
).
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