Transcriptional analysis of Cystic Fibrosis airways at single cell resolution reveals altered epithelial cell states and composition

Details

• Alternative Title:
  Nat Med
• Personal Author:
  Carraro, Gianni ; Langerman, Justin ; Sabri, Shan ; Lorenzana, Zareeb ; Purkayastha, Arunima ; Zhang, Guangzhu ; Konda, Bindu ; Aros, Cody J. ; Calvert, Ben A. ; Szymaniak, Aleks ; Wilson, Emily ; Mulligan, Michael ; Bhatt, Priyanka ; Lu, Junjie ; Vijayaraj, Preethi ; Yao, Changfu ; Shia, David W. ; Lund, Andrew J. ; Israely, Edo ; Rickabaugh, Tammy M. ; Ernst, Jason ; Mense, Martin ; Randell, Scott H. ; Vladar, Eszter K. ; Ryan, Amy L. ; Plath, Kathrin ; Mahoney, John E. ; Stripp, Barry R. ; Gomperts, Brigitte N.
• Description:
  Cystic fibrosis (CF) is a lethal autosomal recessive disorder that afflicts more than 70,000 people. People with CF experience multi-organ dysfunction resulting from aberrant electrolyte transport across polarized epithelia due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF-related lung disease is by far the most important determinant of morbidity and mortality. Here we report results from a multi-institute consortium in which single-cell transcriptomics were applied to define disease-related changes by comparing the proximal airway of CF donors (n = 19) undergoing transplantation for end-stage lung disease with that of previously healthy lung donors (n = 19). Disease-dependent differences observed include an overabundance of epithelial cells transitioning to specialized ciliated and secretory cell subsets coupled with an unexpected decrease in cycling basal cells. Our study yields a molecular atlas of the proximal airway epithelium that will provide insights for the development of new targeted therapies for CF airway disease.
• Subjects:
  Cell Differentiation Cilia Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Epithelial Cells Gene Expression Profiling Humans Lung Respiratory Mucosa Single-Cell Analysis Transcriptome

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• Source:
  Nat Med. 27(5):806-814
• Pubmed ID:
  33958799
• Pubmed Central ID:
  PMC9009537
• Document Type:
  Journal Article
• Funding:
  P01 GM099134/GM/NIGMS NIH HHSUnited States/ ; F31 CA239655/CA/NCI NIH HHSUnited States/ ; KL2 TR001882/TR/NCATS NIH HHSUnited States/ ; P30 DK065988/DK/NIDDK NIH HHSUnited States/ ; DP1 DA044371/DA/NIDA NIH HHSUnited States/ ; T32 GM008042/GM/NIGMS NIH HHSUnited States/ ; HHMI/Howard Hughes Medical InstituteUnited States/ ; R01 CA208303/CA/NCI NIH HHSUnited States/ ; T32 CA009056/CA/NCI NIH HHSUnited States/ ; P01 HL108793/HL/NHLBI NIH HHSUnited States/ ; U66 IP000597/IP/NCIRD CDC HHSUnited States/
• Volume:
  27
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:5966b2cd2f7156d984d90e1941ed98da2cc8dce91b19af291b653ce735e95c31
• Download URL:
  https://stacks.cdc.gov/view/cdc/116473/cdc_116473_DS1.pdf
• File Type:
  [PDF - 6.12 MB ]