Journal: Nature aging

Article Title: Multi-omic rejuvenation and lifespan extension upon exposure to youthful circulation

doi: 10.1038/s43587-023-00451-9

Figure Lengend Snippet: a-c, Principal component analysis (PCA) of CpG methylation across 1,014,243 CpG sites (a), 11,842 promoters (b), and 13,811 gene bodies (c) in n = 36 liver samples and n = 32 blood samples, with 6 different groups in both tissues: young isochronic (Young ISO), young isochronic detached (Young ISO Det.), old heterochronic (Old HET), old isochronic (Old ISO), old heterochronic detached (Old HET Det.), and old isochronic detached (Old ISO Det.). In all the PCA plots, tissue of origin is the largest source of variation (44–91%). d, Mean promoter methylation of Cdc20, Sox30, Mpped1, and Ubl5 across liver RRBS samples. Genes were identified after passing a significance threshold (p < 0.05) when comparing young and old mice, as well as old heterochronic and isochronic mice in both attached and detached groups. Two-tailed Welch’s t-tests were used for statistical analysis. e, Western blot validation (left) and relative protein expression quantification (right) of Sirt3, Gstt2 and C1qb in mice subjected to parabiosis.

Article Snippet: Primary antibodies were as follows: Sirt3 (Cell Signaling Technologies, #5490), C1qb (Novus Biologicals, # NBP2–92455) and Gstt2 (ThermoFisher, # H00002953-D01P) Pan-tubulin (Cell Signaling #2194).

Techniques: Methylation, CpG Methylation Assay, Two Tailed Test, Western Blot, Biomarker Discovery, Expressing

Journal: Nature aging

Article Title: Multi-omic rejuvenation and lifespan extension upon exposure to youthful circulation

doi: 10.1038/s43587-023-00451-9

Figure Lengend Snippet: a–c, Expression of Sirt3 (a), Gstt2 (b) and C1qb (c) in mice subjected to parabiosis by RNA-seq analyses (left), RT–qPCR analyses (middle) and in response to established life span-extending interventions and aging (right). Left: for each gene, normalized expression in logarithmic scale is shown across different parabiosis groups: short-term isochronic (old 1 m ISO, n = 5) and heterochronic (old 1 m HET, n = 5) mice, long-term attached isochronic (old 3 m ISO, n = 3) and heterochronic mice (old 3 m HET, n = 3), long-term detached isochronic (old 3 m detached ISO, n = 3) and heterochronic mice (old 3 m detached HET, n = 3). Adjusted P values, indicating the difference in expression for each pair of isochronic and heterochronic mice, were calculated using a preplanned two-tailed Student’s t-test. The box plots represent the median, 25–75 percentiles and 1.5× IQR. Middle: for the RT–qPCR of each gene, each group has n = 5 biological replicates. The P value between connecting bars was calculated with a two-tailed Student’s t-test. Right: for every signature associated with life span-extending interventions (green) and aging (red), the means of the normalized log fold changes or slopes (for the signatures of the median and maximum life span) are presented. The error bars denote ± 1 s.e. Adjusted P values, indicating the difference of expression change from zero, were calculated with a mixed-effect linear model.

Article Snippet: Primary antibodies were as follows: Sirt3 (Cell Signaling Technologies, #5490), C1qb (Novus Biologicals, # NBP2–92455) and Gstt2 (ThermoFisher, # H00002953-D01P) Pan-tubulin (Cell Signaling #2194).

Techniques: Expressing, RNA Sequencing, Quantitative RT-PCR, Two Tailed Test

Journal: BMC Medical Genetics

Article Title: Association of C1QB gene polymorphism with schizophrenia in Armenian population

doi: 10.1186/1471-2350-12-126

Figure Lengend Snippet: Distribution of C1QA/C1QB genotypes and carriage of minor alleles in patients with schizophrenia (SCZ) and healthy subjects (Controls).

Article Snippet: Genotypes for C1QB rs913243G/T SNP were determined using TaqMan SNP genotyping assay (Applied Biosystems, Assay ID C_3176751_10) according to the manufacturer's instruction.

Techniques:

Journal: BMC Medical Genetics

Article Title: Association of C1QB gene polymorphism with schizophrenia in Armenian population

doi: 10.1186/1471-2350-12-126

Figure Lengend Snippet: LD blocks of C1QB gene rs913243/rs291982/rs631090 SNPs and values of absolute D' as well as r 2 for patients with schizophrenia (SCZ) and healthy subjects (Controls) .

Article Snippet: Genotypes for C1QB rs913243G/T SNP were determined using TaqMan SNP genotyping assay (Applied Biosystems, Assay ID C_3176751_10) according to the manufacturer's instruction.

Techniques:

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Complement C1q mediates the expansion of periportal hepatic progenitor cells in senescence-associated inflammatory liver

doi: 10.1073/pnas.1918028117

Figure Lengend Snippet: Complement C1q levels are elevated in the inflammatory niche and associated with activation of the β-catenin pathway in periportal HPCs. (A) Results of the microarray analysis showing the levels of the C1qa, C1qb, and C1qc mRNAs in liver tissues collected from WT control and β-catenin KO mice at the indicated ages. The levels were compared with the 2- to 3-mo-old WT livers, in which the level was set to 1. n = 3 to 6 per group. (B and C) qRT-PCR data (B) and representative Western blots (C) showing C1q expression in the liver tissues of WT and β-catenin KO mice at various ages. Levels of C1qa, C1qb, and C1qc mRNA were compared between the β-catenin KO livers and WT livers at 2 to 4 mo. Results are presented as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001. n = 3 to 5 per group. (D) IHC staining with C1q antibody in the liver tissues collected from 2- and 10-mo-old WT and β-catenin KO mice. (E) IF staining for C1q, F4/80, and CD11b in liver tissues of 10-mo-old β-catenin KO mice. White arrowheads indicate the colocalization of C1q and F4/80. (F–I) Representative IF and IHC staining with indicated antibodies in 10- to 12-mo-old β-catenin KO liver tissues. (Scale bars: 50 µm.)

Article Snippet: Instead, a prominent elevation in the expression levels of complement component C1q (including subunits C1qa, C1qb, and C1qc) was commonly identified in the livers of 10- and 18-mo-old β-catenin KO mice by Biocarta, GeneMAPP, and KEGG analyses ( SI Appendix , Table S1 and ).

Techniques: Activation Assay, Microarray, Quantitative RT-PCR, Western Blot, Expressing, Immunohistochemistry, Staining

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Complement C1q mediates the expansion of periportal hepatic progenitor cells in senescence-associated inflammatory liver

doi: 10.1073/pnas.1918028117

Figure Lengend Snippet: Inhibition of C1q suppresses the expansion of periportal HPCs in β-catenin KO mice. (A) C3a levels in serum samples collected from β-catenin KO mice before (7 mo) and after (9 mo) 2J peptide treatment, as determined by enzyme-linked immunosorbent assay. (B) Representative images of the gross view, liver weights (Left) and liver-to-body weight ratios (Right) of 9-mo-old β-catenin KO mice with and without 2J peptide treatment. (C) Representative images of IF staining for the indicated antibodies in continuous liver tissue sections collected from 9-mo-old β-catenin KO mice with and without 2J peptide treatment. Percentages of β-catenin (+) and GS(+) areas were quantified and are shown in bar graphs to the right of the staining results. (D) Western blots showing the expression of β-catenin and GS in liver tissues collected from 9-mo-old β-catenin KO mice with and without 2J peptide treatment. β-catenin and GS expression in the liver tissues from age-matched WT control mice served as a positive control. (E) Genomic DNA was extracted from liver tissues collected from untreated and 2J peptide-treated β-catenin KO mice and processed for qRT-PCR analysis using primer sets that differentiated the occurrence of Cre-loxP recombination to examine the percentage of cells in which β-catenin was deleted in each liver tissue. The percentage observed in the livers of 2-mo-old β-catenin KO mice was set to 100%. (F) Representative IHC staining for GS in the liver tissues collected from 9-mo-old WT mice treated with PBS, DXS, or 2J peptide. (G) Western blot showing the expression of β-catenin and GS in the liver tissues of WT mice treated with indicated inhibitors. (H) C3a levels in serum samples collected from WT mice after treatment with PBS, DXS, and 2J peptide. Results are presented as mean ± SD. N.S., not significant. *P < 0.05; **P < 0.01; ***P < 0.001. (Scale bars: 1 cm for B; 200 µm for C and F.)

Article Snippet: Instead, a prominent elevation in the expression levels of complement component C1q (including subunits C1qa, C1qb, and C1qc) was commonly identified in the livers of 10- and 18-mo-old β-catenin KO mice by Biocarta, GeneMAPP, and KEGG analyses ( SI Appendix , Table S1 and ).

Techniques: Inhibition, Enzyme-linked Immunosorbent Assay, Staining, Western Blot, Expressing, Positive Control, Quantitative RT-PCR, Immunohistochemistry

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Complement C1q mediates the expansion of periportal hepatic progenitor cells in senescence-associated inflammatory liver

doi: 10.1073/pnas.1918028117

Figure Lengend Snippet: Liver tumors containing WT β-catenin are responsive to C1q inhibitor treatment. (A and B) Representative images of H&E and IHC staining for Ki67 (A) and β-catenin (B) in WT and mutant β-catenin–containing liver tumors from β-catenin KO and HBx-Tg/β-catenin KO mice that were not treated or treated with 2J peptide for 2 mo. Percentages of positive signals for Ki67 and β-catenin were quantified and are shown as bar graphs to the right of the images. (C) Western blots showing the expression of β-catenin in WT and mutant β-catenin–containing liver tumors collected from untreated or 2J peptide-treated tumor-bearing mice. β-catenin expression in the liver tissues of WT control mice served as a positive control. (D) Genomic DNA extracted from the liver tissues collected from different groups of mice as indicated were processed for qRT-PCR analysis to evaluate the percentage of cells in which β-catenin was deleted in each liver tissue. The percentage of β-catenin depletion in the liver tissues from 2-mo-old β-catenin KO mice was set to 100%. The β-catenin mutations identified in the tumors were mutations or deletions at around exon 3 of the CTNNB1 gene. Results are presented as mean ± SD. N.S., not significant. ***P < 0.001. (Scale bar: 50 µm for A and B.)

Article Snippet: Instead, a prominent elevation in the expression levels of complement component C1q (including subunits C1qa, C1qb, and C1qc) was commonly identified in the livers of 10- and 18-mo-old β-catenin KO mice by Biocarta, GeneMAPP, and KEGG analyses ( SI Appendix , Table S1 and ).

Techniques: Immunohistochemistry, Mutagenesis, Western Blot, Expressing, Positive Control, Quantitative RT-PCR

Journal: Proceedings of the National Academy of Sciences of the United States of America

Article Title: Complement C1q mediates the expansion of periportal hepatic progenitor cells in senescence-associated inflammatory liver

doi: 10.1073/pnas.1918028117

Figure Lengend Snippet: Abundant C1q-expressing inflammatory cells are present in the nontumor regions of liver tissues from patients with viral infection-related HCC. (A) qRT-PCR of C1q in the nontumor and tumor liver tissues collected from patients with HBV- and HCV-related HCC. The nontumor liver tissues collected from patients with hemangioma or FNH were included as normal liver controls. Results are presented as mean ± SD. *P < 0.05; ***P < 0.001. (B and C) Representative images of H&E and IHC staining for C1q (B) and CK19 (C) in the normal liver tissues and nontumorous liver tissues from patients with HBV- and HCV-related HCC. (D) Association between the mRNA levels of C1q and p21 in the nontumor liver tissues of patients with HBV- and HCV-related HCC. (E) Representative images of the H&E and IHC staining for GS, CK19, and C1q in the paired nontumorous (NT) and tumorous (T) liver tissues collected from patients with HBV- and HCV-related HCC. (Scale bars: 50 µm for B and C; 100 µm for E.)

Article Snippet: Instead, a prominent elevation in the expression levels of complement component C1q (including subunits C1qa, C1qb, and C1qc) was commonly identified in the livers of 10- and 18-mo-old β-catenin KO mice by Biocarta, GeneMAPP, and KEGG analyses ( SI Appendix , Table S1 and ).

Techniques: Expressing, Infection, Quantitative RT-PCR, Immunohistochemistry