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Article | Tang Xiaotang’s epigenome can maintain a specific chromatin state for a long period of time, and even achieve long-lasting information storage across several generations of cells.
Its core role in regulating basic life processes has been explained to a certain extent [ 1]
.
However, in the process of immune response (such as vaccine induction), how cell heterogeneity affects the epitranscriptome is still unclear, and there is a lack of comprehensive systems biology assessment of the epigenome landscape at the single-cell level
.
On June 25, 2021, the Bali Pulendran team of Stanford University published a research paper entitled The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination online on Cell.
At the single-cell level, including EpiTOF and ATAC-seq And scRNA-seq technology, drawn the epigenome and transcription panorama of human influenza vaccine immunity
.
Researchers first used EpiTOF to analyze a cohort of 21 healthy people aged 18-45 years old before and after influenza vaccination.
The analysis included the 21st and 0th days before vaccination, and the 1, 7, 30, and 180 days after vaccination.
Days of PBMCs, it was found that the proportion of immune cell population did not change significantly between these time points
.
The histone modification UMAP landscape of each subgroup clearly shows that lymphocytes and myeloid lines are separated, hematopoietic progenitor cells (CD34+) are separated from fully differentiated immune cells, and samples at different time points are also separated.
The 30-day change was more obvious.
Compared with the baseline level, the histone methylation markers in CD34+ cells increased and the acetylation markers in the myeloid system decreased
.
The modification of H2BK5ac, H3K9ac, H3K27ac and H4K5ac on the 30th day of classical monocytes and myeloid dendritic cells (mDCs) is inhibited
.
By clustering and analyzing mDCs and classical monocytes using H3K27ac, H2BK5ac, H4K5ac, H3K9ac, and PADI4 markers, the researchers constructed a single-cell histone modification panorama and found that the cells on day 180 did not return to the baseline position.
It is in an intermediate state, which indicates that persistent epigenetic changes can be detected within 6 months of flu vaccination
.
Then, the researchers used LPS, Flagellin, Pam-3-Cys or pI:C, R848 to stimulate PBMCs at different time points before or after vaccination
.
It was found that some cytokines and chemokines decreased significantly from day 1 to day 7 after vaccination, reached their lowest point on day 30, and returned to near baseline levels on day 180
.
The researchers used paired correlation analysis to correlate the levels of cytokines in the samples with the levels of EpiTOF histone modifications in classical monocytes, as well as the proportion of monocytes and cell viability in PBMCs of the same sample, and found that histone acetylation markers are associated with cells Factor secretion is positively correlated, and inhibitory methylation markers are negatively correlated with cytokine secretion, and the causal relationship is proved by adding enzymes and inhibitors
.
Furthermore, the researchers found through ATAC-seq analysis that after vaccination, the accessibility of chromatin at AP-1 targeted sites in the myeloid lineage was reduced, and constructed innate immune cells after vaccination through scATAC-seq and scRNA-seq The panorama has determined its chromatin accessibility and the heterogeneity of transcription levels
.
Finally, the researchers used EpiTOF to analyze the PBMC samples of 18 vaccinators (9 H5N1, 9 H5N1+AS03) on days 0, 7, 21, 28, and 42, and constructed histone modification spectra.
It was found that after inoculation with H5N1+AS03 (but not H5N1), H3K27ac, H4K5ac, H3K9ac and PADI4 in classical monocytes were significantly reduced, and the production of innate cytokines and chemokines was also significantly reduced.
The scATAC-seq results showed AP-1 Chromatin accessibility has also decreased, but the chromatin accessibility of TFs in the IRF and STAT families has increased, indicating that the antiviral response may have been enhanced, as evidenced by dengue virus or Zika virus infection of PBMCs in vitro After infection, the virus titer decreases early, and it is related to the changes in the expression of antiviral genes related to the open chromatin induced by the vaccine
.
In general, this study has mapped the epigenome and transcriptome of human influenza vaccine immunity at the single-cell level
.
After vaccination, the chromatin accessibility of IRF sites in classical monocytes and mDCs continues to increase, which is related to the increase in the expression of antiviral genes, and may increase resistance to unrelated Zika virus and dengue virus Contribution, therefore vaccination induces a continuous epigenomic remodeling of the innate immune system
.
Original address: https://doi.
org/10.
1016/j.
cell.
2021.
05.
039 Platemaker: 11 References 1.
Allis, CD, and Jenuwein, T.
(2016).
The molecular hallmarks of epigenetic control.
Nat .
Rev.
Genet.
17, 487–500.
Reprinting instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
Its core role in regulating basic life processes has been explained to a certain extent [ 1]
.
However, in the process of immune response (such as vaccine induction), how cell heterogeneity affects the epitranscriptome is still unclear, and there is a lack of comprehensive systems biology assessment of the epigenome landscape at the single-cell level
.
On June 25, 2021, the Bali Pulendran team of Stanford University published a research paper entitled The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination online on Cell.
At the single-cell level, including EpiTOF and ATAC-seq And scRNA-seq technology, drawn the epigenome and transcription panorama of human influenza vaccine immunity
.
Researchers first used EpiTOF to analyze a cohort of 21 healthy people aged 18-45 years old before and after influenza vaccination.
The analysis included the 21st and 0th days before vaccination, and the 1, 7, 30, and 180 days after vaccination.
Days of PBMCs, it was found that the proportion of immune cell population did not change significantly between these time points
.
The histone modification UMAP landscape of each subgroup clearly shows that lymphocytes and myeloid lines are separated, hematopoietic progenitor cells (CD34+) are separated from fully differentiated immune cells, and samples at different time points are also separated.
The 30-day change was more obvious.
Compared with the baseline level, the histone methylation markers in CD34+ cells increased and the acetylation markers in the myeloid system decreased
.
The modification of H2BK5ac, H3K9ac, H3K27ac and H4K5ac on the 30th day of classical monocytes and myeloid dendritic cells (mDCs) is inhibited
.
By clustering and analyzing mDCs and classical monocytes using H3K27ac, H2BK5ac, H4K5ac, H3K9ac, and PADI4 markers, the researchers constructed a single-cell histone modification panorama and found that the cells on day 180 did not return to the baseline position.
It is in an intermediate state, which indicates that persistent epigenetic changes can be detected within 6 months of flu vaccination
.
Then, the researchers used LPS, Flagellin, Pam-3-Cys or pI:C, R848 to stimulate PBMCs at different time points before or after vaccination
.
It was found that some cytokines and chemokines decreased significantly from day 1 to day 7 after vaccination, reached their lowest point on day 30, and returned to near baseline levels on day 180
.
The researchers used paired correlation analysis to correlate the levels of cytokines in the samples with the levels of EpiTOF histone modifications in classical monocytes, as well as the proportion of monocytes and cell viability in PBMCs of the same sample, and found that histone acetylation markers are associated with cells Factor secretion is positively correlated, and inhibitory methylation markers are negatively correlated with cytokine secretion, and the causal relationship is proved by adding enzymes and inhibitors
.
Furthermore, the researchers found through ATAC-seq analysis that after vaccination, the accessibility of chromatin at AP-1 targeted sites in the myeloid lineage was reduced, and constructed innate immune cells after vaccination through scATAC-seq and scRNA-seq The panorama has determined its chromatin accessibility and the heterogeneity of transcription levels
.
Finally, the researchers used EpiTOF to analyze the PBMC samples of 18 vaccinators (9 H5N1, 9 H5N1+AS03) on days 0, 7, 21, 28, and 42, and constructed histone modification spectra.
It was found that after inoculation with H5N1+AS03 (but not H5N1), H3K27ac, H4K5ac, H3K9ac and PADI4 in classical monocytes were significantly reduced, and the production of innate cytokines and chemokines was also significantly reduced.
The scATAC-seq results showed AP-1 Chromatin accessibility has also decreased, but the chromatin accessibility of TFs in the IRF and STAT families has increased, indicating that the antiviral response may have been enhanced, as evidenced by dengue virus or Zika virus infection of PBMCs in vitro After infection, the virus titer decreases early, and it is related to the changes in the expression of antiviral genes related to the open chromatin induced by the vaccine
.
In general, this study has mapped the epigenome and transcriptome of human influenza vaccine immunity at the single-cell level
.
After vaccination, the chromatin accessibility of IRF sites in classical monocytes and mDCs continues to increase, which is related to the increase in the expression of antiviral genes, and may increase resistance to unrelated Zika virus and dengue virus Contribution, therefore vaccination induces a continuous epigenomic remodeling of the innate immune system
.
Original address: https://doi.
org/10.
1016/j.
cell.
2021.
05.
039 Platemaker: 11 References 1.
Allis, CD, and Jenuwein, T.
(2016).
The molecular hallmarks of epigenetic control.
Nat .
Rev.
Genet.
17, 487–500.
Reprinting instructions [Original Articles] BioArt original articles are welcome to be shared by individuals.
Reprinting is prohibited without permission.
The copyrights of all published works are owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
