Multiomic Profiling of Human Clonal Hematopoiesis Reveals Genotype and Cell-Specific Inflammatory Pathway Activation

Details

• Personal Author:
  Ahmad A ; Bhat P ; Bick AG ; Brown D ; Ferrell PB ; Heimlich JB ; Hu N ; Jenkins MT ; Olson S ; Parker AC ; Potts CR ; Savona MR ; Sharber B ; Silver AJ ; Ulloa J ; Van Amburg JC ; van Galen P ; Vlasschaert C
• Description:
  Clonal hematopoiesis (CH) is an age-associated phenomenon that increases the risk of hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood.1 Here, we profile peripheral blood gene expression in 66 968 single cells from a cohort of 17 patients with CH and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutant Tet methylcytosine dioxygenase 2 (TET2) and DNA methyltransferase 3A (DNMT3A) cells with nonmutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment. Additionally, patients harboring DNMT3A and TET2 CH mutations possessed a proinflammatory profile in CD14+ monocytes through previously unrecognized pathways such as galectin and macrophage inhibitory factor. We also found that T cells from patients with CH, although mostly unmutated, had decreased expression of GTPase of the immunity associated protein genes, which are critical to T-cell development, suggesting that CH impairs T-cell function. [Description provided by NIOSH]
• Subjects:
  Aging Blood Hematologic Tests Immune System Occupational Health Safety
• Keywords:
  Blood Cells Cytokines Gene Expression Hematology Hematopoiesis Immunology
• ISSN:
  2473-9529
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; New York ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 4 ; Tennessee
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  8
• Issue:
  14
• NIOSHTIC Number:
  nn:20070833
• Citation:
  Blood Adv 2024 Jul; 8(14):3665-3678
• Contact Point Address:
  Alexander G. Bick, Vanderbilt University Medical Center, 2200 Pierce Ave, Nashville, TN 37232
• Email:
  alexander.bick@vumc.org
• Federal Fiscal Year:
  2024
• Performing Organization:
  Albert Einstein College of Medicine, Bronx, New York
• Peer Reviewed:
  True
• Start Date:
  20210701
• Source Full Name:
  Blood Advances
• End Date:
  20240630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e6765cb8912bf07299a0a8025092ddd2ab565d70cdd9d00d72941f75552f383e2dceb69b6067876aa7010ec8c89512fad41beaa1b37128f82a890277fe078b90
• Download URL:
  https://stacks.cdc.gov/view/cdc/208981/cdc_208981_DS1.pdf
• File Type:
  [PDF - 2.82 MB ]