Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells.

Bibliographic Details
Title: Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells.
Authors: Saigusa, Ryosuke, Vallejo, Jenifer, Gulati, Rishab, Suthahar, Sujit Silas Armstrong, Suryawanshi, Vasantika, Alimadadi, Ahmad, Makings, Jeffrey, Durant, Christopher P., Freuchet, Antoine, Roy, Payel, Ghosheh, Yanal, Pandori, William, Pattarabanjird, Tanyaporn, Drago, Fabrizio, Taylor, Angela, McNamara, Coleen A., Shemesh, Avishai, Lanier, Lewis L., Hedrick, Catherine C., Ley, Klaus
Source: International Journal of Molecular Sciences; Sep2022, Vol. 23 Issue 17, p9875, 21p
Subject Terms: CORONARY artery disease, MONONUCLEAR leukocytes, CD4 antigen, RISK perception, PEOPLE with diabetes, GERM cells, SEX (Biology)
Abstract: Despite the decades-old knowledge that males and people with diabetes mellitus (DM) are at increased risk for coronary artery disease (CAD), the reasons for this association are only partially understood. Among the immune cells involved, recent evidence supports a critical role of T cells as drivers and modifiers of CAD. CD4+ T cells are commonly found in atherosclerotic plaques. We aimed to understand the relationship of CAD with sex and DM by single-cell RNA (scRNA-Seq) and antibody sequencing (CITE-Seq) of CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by scRNA-Seq combined with 49 surface markers (CITE-Seq). CAD severity was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD−. Four pairs of groups were matched for clinical and demographic parameters. To test how sex and DM changed cell proportions and gene expression, we compared matched groups of men and women, as well as diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 16 women and 45 men with and without coronary artery disease and with and without DM. We identified 16 clusters in CD4+ T cells. The proportion of cells in CD4+ effector memory cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. This same cluster, CD4T8, was significantly decreased in female participants, along with two other CD4+ T cell clusters. In CD4+ T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature. We conclude that (1) CAD and DM are clearly reflected in PBMC transcriptomes, and (2) significant differences exist between women and men and (3) between subjects with DM and non-DM. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells.
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  Data: <searchLink fieldCode="AR" term="%22Saigusa%2C+Ryosuke%22">Saigusa, Ryosuke</searchLink><br /><searchLink fieldCode="AR" term="%22Vallejo%2C+Jenifer%22">Vallejo, Jenifer</searchLink><br /><searchLink fieldCode="AR" term="%22Gulati%2C+Rishab%22">Gulati, Rishab</searchLink><br /><searchLink fieldCode="AR" term="%22Suthahar%2C+Sujit+Silas+Armstrong%22">Suthahar, Sujit Silas Armstrong</searchLink><br /><searchLink fieldCode="AR" term="%22Suryawanshi%2C+Vasantika%22">Suryawanshi, Vasantika</searchLink><br /><searchLink fieldCode="AR" term="%22Alimadadi%2C+Ahmad%22">Alimadadi, Ahmad</searchLink><br /><searchLink fieldCode="AR" term="%22Makings%2C+Jeffrey%22">Makings, Jeffrey</searchLink><br /><searchLink fieldCode="AR" term="%22Durant%2C+Christopher+P%2E%22">Durant, Christopher P.</searchLink><br /><searchLink fieldCode="AR" term="%22Freuchet%2C+Antoine%22">Freuchet, Antoine</searchLink><br /><searchLink fieldCode="AR" term="%22Roy%2C+Payel%22">Roy, Payel</searchLink><br /><searchLink fieldCode="AR" term="%22Ghosheh%2C+Yanal%22">Ghosheh, Yanal</searchLink><br /><searchLink fieldCode="AR" term="%22Pandori%2C+William%22">Pandori, William</searchLink><br /><searchLink fieldCode="AR" term="%22Pattarabanjird%2C+Tanyaporn%22">Pattarabanjird, Tanyaporn</searchLink><br /><searchLink fieldCode="AR" term="%22Drago%2C+Fabrizio%22">Drago, Fabrizio</searchLink><br /><searchLink fieldCode="AR" term="%22Taylor%2C+Angela%22">Taylor, Angela</searchLink><br /><searchLink fieldCode="AR" term="%22McNamara%2C+Coleen+A%2E%22">McNamara, Coleen A.</searchLink><br /><searchLink fieldCode="AR" term="%22Shemesh%2C+Avishai%22">Shemesh, Avishai</searchLink><br /><searchLink fieldCode="AR" term="%22Lanier%2C+Lewis+L%2E%22">Lanier, Lewis L.</searchLink><br /><searchLink fieldCode="AR" term="%22Hedrick%2C+Catherine+C%2E%22">Hedrick, Catherine C.</searchLink><br /><searchLink fieldCode="AR" term="%22Ley%2C+Klaus%22">Ley, Klaus</searchLink>
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  Data: International Journal of Molecular Sciences; Sep2022, Vol. 23 Issue 17, p9875, 21p
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  Data: <searchLink fieldCode="DE" term="%22CORONARY+artery+disease%22">CORONARY artery disease</searchLink><br /><searchLink fieldCode="DE" term="%22MONONUCLEAR+leukocytes%22">MONONUCLEAR leukocytes</searchLink><br /><searchLink fieldCode="DE" term="%22CD4+antigen%22">CD4 antigen</searchLink><br /><searchLink fieldCode="DE" term="%22RISK+perception%22">RISK perception</searchLink><br /><searchLink fieldCode="DE" term="%22PEOPLE+with+diabetes%22">PEOPLE with diabetes</searchLink><br /><searchLink fieldCode="DE" term="%22GERM+cells%22">GERM cells</searchLink><br /><searchLink fieldCode="DE" term="%22SEX+%28Biology%29%22">SEX (Biology)</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Despite the decades-old knowledge that males and people with diabetes mellitus (DM) are at increased risk for coronary artery disease (CAD), the reasons for this association are only partially understood. Among the immune cells involved, recent evidence supports a critical role of T cells as drivers and modifiers of CAD. CD4+ T cells are commonly found in atherosclerotic plaques. We aimed to understand the relationship of CAD with sex and DM by single-cell RNA (scRNA-Seq) and antibody sequencing (CITE-Seq) of CD4+ T cells. Peripheral blood mononuclear cells (PBMCs) of 61 men and women who underwent cardiac catheterization were interrogated by scRNA-Seq combined with 49 surface markers (CITE-Seq). CAD severity was quantified using Gensini scores, with scores above 30 considered CAD+ and below 6 considered CAD−. Four pairs of groups were matched for clinical and demographic parameters. To test how sex and DM changed cell proportions and gene expression, we compared matched groups of men and women, as well as diabetic and non-diabetic subjects. We analyzed 41,782 single CD4+ T cell transcriptomes for sex differences in 16 women and 45 men with and without coronary artery disease and with and without DM. We identified 16 clusters in CD4+ T cells. The proportion of cells in CD4+ effector memory cluster 8 (CD4T8, CCR2+ Em) was significantly decreased in CAD+, especially among DM+ participants. This same cluster, CD4T8, was significantly decreased in female participants, along with two other CD4+ T cell clusters. In CD4+ T cells, 31 genes showed significant and coordinated upregulation in both CAD and DM. The DM gene signature was partially additive to the CAD gene signature. We conclude that (1) CAD and DM are clearly reflected in PBMC transcriptomes, and (2) significant differences exist between women and men and (3) between subjects with DM and non-DM. [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.3390/ijms23179875
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        Text: English
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        Type: general
      – SubjectFull: MONONUCLEAR leukocytes
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      – SubjectFull: SEX (Biology)
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