The discovery of Lgr5+ intestinal stem cells (ISCs) triggered a breakthrough in the field of ISC research. Lgr5+ ISCs maintain the homeostasis of the intestinal epithelium in the steady state, while ...these cells are susceptible to epithelial damage induced by chemicals, pathogens, or irradiation. During the regeneration process of the intestinal epithelium, more quiescent +4 stem cells and short-lived transit-amplifying (TA) progenitor cells residing above Lgr5+ ISCs undergo dedifferentiation and act as stem-like cells. In addition, several recent reports have shown that a subset of terminally differentiated cells, including Paneth cells, tuft cells, or enteroendocrine cells, may also have some degree of plasticity in specific situations. The function of ISCs is maintained by the neighboring stem cell niches, which strictly regulate the key signal pathways in ISCs. In addition, various inflammatory cytokines play critical roles in intestinal regeneration and stem cell functions following epithelial injury. Here, we summarize the current understanding of ISCs and their niches, review recent findings regarding cellular plasticity and its regulatory mechanism, and discuss how inflammatory cytokines contribute to epithelial regeneration.
Infant gut microbiota development affects the host physiology throughout life, and short-chain fatty acids (SCFAs) are promising key metabolites mediating microbiota-host relationships. Here, we ...investigated dense longitudinally collected faecal samples from 12 subjects during the first 2 years (n = 1048) to identify early life gut SCFA patterns and their relationships with the microbiota. Our results revealed three distinct phases of progression in the SCFA profiles: early phase characterised by low acetate and high succinate, middle-phase characterised by high lactate and formate and late-phase characterised by high propionate and butyrate. Assessment of the SCFA-microbiota relationships revealed that faecal butyrate is associated with increased Clostridiales and breastfeeding cessation, and that diverse and personalised assemblage of Clostridiales species possessing the acetyl-CoA pathway play major roles in gut butyrate production. We also found an association between gut formate and some infant-type bifidobacterial species, and that human milk oligosaccharides (HMO)-derived fucose is the substrate for formate production during breastfeeding. We identified genes upregulated in fucose and fucosylated HMO utilisation in infant-type bifidobacteria. Notably, bifidobacteria showed interspecific and intraspecific variation in the gene repertoires, and cross-feeding of fucose contributed to gut formate production. This study provides an insight into early life SCFA-microbiota relationships, which is an important step for developing strategies for modulating lifelong health.
Recent studies have demonstrated that gut microbiota development influences infants' health and subsequent host physiology. However, the factors shaping the development of the microbiota remain ...poorly understood, and the mechanisms through which these factors affect gut metabolite profiles have not been extensively investigated. Here we analyse gut microbiota development of 27 infants during the first month of life. We find three distinct clusters that transition towards Bifidobacteriaceae-dominant microbiota. We observe considerable differences in human milk oligosaccharide utilization among infant bifidobacteria. Colonization of fucosyllactose (FL)-utilizing bifidobacteria is associated with altered metabolite profiles and microbiota compositions, which have been previously shown to affect infant health. Genome analysis of infants' bifidobacteria reveals an ABC transporter as a key genetic factor for FL utilization. Thus, the ability of bifidobacteria to utilize FL and the presence of FL in breast milk may affect the development of the gut microbiota in infants, and might ultimately have therapeutic implications.
The human skin microbiome can vary over time, and inter-individual variability of the microbiome is greater than the temporal variability within an individual. The skin microbiome has become a useful ...tool to identify individuals, and one type of personal identification using the skin microbiome has been reported in a community of less than 20 individuals. However, identification of individuals based on the skin microbiome has shown low accuracy in communities larger than 80 individuals. Here, we developed a new approach for personal identification, which considers that minor taxa are one of the important factors for distinguishing between individuals. We originally established a human skin microbiome for 66 samples from 11 individuals over two years (33 samples each year). Our method could classify individuals with 85% accuracy beyond a one-year sampling period. Moreover, we applied our method to 837 publicly available skin microbiome samples from 89 individuals and succeeded in identifying individuals with 78% accuracy. In short, our results investigate that (i) our new personal identification method worked well with two different communities (our data: 11 individuals; public data: 89 individuals) using the skin microbiome, (ii) defining the personal skin microbiome requires samples from several time points, (iii) inclusion of minor skin taxa strongly contributes to the effectiveness of personal identification.
After complete sequencing of a number of genomes the focus has now turned to proteomics. Advanced proteomics technologies such as two-hybrid assay, mass spectrometry etc. are producing huge data sets ...of protein-protein interactions which can be portrayed as networks, and one of the burning issues is to find protein complexes in such networks. The enormous size of protein-protein interaction (PPI) networks warrants development of efficient computational methods for extraction of significant complexes.
This paper presents an algorithm for detection of protein complexes in large interaction networks. In a PPI network, a node represents a protein and an edge represents an interaction. The input to the algorithm is the associated matrix of an interaction network and the outputs are protein complexes. The complexes are determined by way of finding clusters, i. e. the densely connected regions in the network. We also show and analyze some protein complexes generated by the proposed algorithm from typical PPI networks of Escherichia coli and Saccharomyces cerevisiae. A comparison between a PPI and a random network is also performed in the context of the proposed algorithm.
The proposed algorithm makes it possible to detect clusters of proteins in PPI networks which mostly represent molecular biological functional units. Therefore, protein complexes determined solely based on interaction data can help us to predict the functions of proteins, and they are also useful to understand and explain certain biological processes.
The gastric oxyntic glands are maintained by gastric stem cells that continuously supply all differentiated cell types within the corpus epithelium. Stem cells are supported by stromal cells that ...make up the stem cell niche. In this issue of the JCI, Fischer et al. report on their use of genetically engineered mouse models and organoids to study the role of R-spondin 3 (RSPO3) in the stomach. RSPO3, one of the major stem cell niche factors, primarily promoted secretory differentiation in the normal stomach, but also contributed to regeneration following injury. Mechanistically, RSPO3 was upregulated in the stroma by loss of chief cells and then activated the YAP pathway in gastric stem and progenitor cells, which appeared to be critical for regeneration of the secretory lineage. These data substantially advance our understanding of the regulation of gastric stem cells and highlight a function for RSPO3 in the gastrointestinal tract, which is as the gatekeeper of secretory differentiation.
Abstract
Summary
: Similarity searches of amino acid sequences against the public metagenomic data can provide users insights about the function of sequences based on the environmental distribution ...of similar sequences. However, a considerable reduction in the amount of data or the accuracy of the result was necessary to conduct sequence similarity searches against public metagenomic data, because of the vast data size more than Terabytes. Here, we present an ultra-fast service for the highly accurate amino acid sequence similarity search, called PZLAST, which can search the user’s amino acid sequences to several Terabytes of public metagenomic sequences in ∼10–20 min. PZLAST accomplishes its search speed by using PEZY-SC2, which is a Multiple Instruction Multiple Data many-core processor. Results of PZLAST are summarized by the ontology-based environmental distribution of similar sequences. PZLAST can be used to predict the function of sequences and mine for homologs of functionally important gene sequences.
Availability and implementation
PZLAST is freely accessible at https://pzlast.riken.jp/meta without requiring registration.
Supplementary information
Supplementary data are available at Bioinformatics online.
Summary
The production of renewable bioenergy will be necessary to meet rising global fossil fuel demands. Members of the marine microalgae genus Nannochloropsis produce large quantities of oils ...(triacylglycerols; TAGs), and this genus is regarded as one of the most promising for biodiesel production. Recent genome sequencing and transcriptomic studies on Nannochloropsis have provided a foundation for understanding its oleaginous trait, but the mechanism underlying oil accumulation remains to be clarified. Here we report Nannochloropsis knock‐out strains of four extraplastidic lysophosphatidic acid acyltransferases (LPAT1–LPAT4) that catalyze a major de novo biosynthetic step of TAGs and membrane lipids. We found that the four LPATs are differently involved in lipid metabolic flow in Nannochloropsis. Double knock‐outs among the LPATs revealed the pivotal LPATs for TAG biosynthesis, and localization analysis indicated that the stramenopile‐specific LPATs (LPAT3 and LPAT4) associated with TAG synthesis reside at the perimeter of lipid droplets. No homologous region has been found with other lipid droplet‐associated proteins, however. Lipid droplets are an organelle found in nearly all organisms, and recently they were shown to play important roles in cellular metabolism and signaling. Our results provide direct evidence for the importance of the perimeter of lipid droplet in TAG synthesis in addition to its known role in maintaining TAG stability, and these findings suggest that the oleaginous trait of Nannochloropsis is enabled by the acquisition of LPATs at the perimeter of lipid droplets.
Significance Statement
We have identified the main enzymes, called lysophosphatidic acid acyltransferases, of oleaginous alga Nannochloropsis that are central players for production of utilizable triacylglycerols. Intriguingly, two of these acyltransferases are located at the perimeter of lipid droplets, which are found in nearly all organisms, and these droplets have recently been shown to play important roles in cellular metabolism and signaling.
Background
Drug resistance in colorectal cancers is assumed to be mediated by changes in the expression of microRNAs, but the specific identities and roles of microRNAs are largely unclear. We ...examined the effect of 5-fluorouracil (5-FU) resistance on microRNA expression.
Methods
Two types of 5-FU-resistant colon cancer cells were derived from the DLD-1 and KM12C cell lines. The expressions of microRNAs were profiled with a microarray containing 723 microRNAs and validated by quantitative real-time polymerase chain reaction (qRT-PCR). To survey the downstream mediators of microRNA, we used a microRNA:mRNA immunoprecipitation (RIP)-Chip and pathway analysis tool to identify potential direct targets of microRNA.
Results
In response to 5-FU, miR-19b and miR-21 were over-expressed in 5-FU-resistant cells. Of note, miR-19b was up-regulated 3.47-fold in the DLD-1 resistant cells, which exhibited no alteration in cell cycle profiles despite exposure to 5-FU. After transfection of miR-19b, specific mRNAs were recruited to microRNA:mRNA complexes isolated with Ago2 antibody and subjected to whole-genome transcriptional analysis. In this analysis, 66 target mRNAs were enriched by at least 5.0-fold in the microRNA:mRNA complexes from DLD-1 resistant cells. Ingenuity pathway analysis of mRNA targets significantly (
P
< 0.05) indicated the category “Cell Cycle” as a probable area of the molecular and cellular function related with 5-FU resistance. Among candidate mRNA targets,
SFPQ
and
MYBL2
have been linked to cell cycle functions.
Conclusions
We revealed up-regulation of miR-19b in response to 5-FU and potential targets of miR-19b mediating the cell cycle under treatment with 5-FU. Our study provides an important insight into the mechanism of 5-FU resistance in colorectal cancers.
PDF
