Single-cell chromatin accessibility and transposable element landscapes reveal shared features of tissue-residing immune cells

• Published in: Immunity (Cambridge, Mass.) Vol. 57; no. 8; pp. 1975 - 1993.e10
• Main Authors: Simon, Malte, Stüve, Philipp, Schmidleithner, Lisa, Bittner, Sebastian, Beumer, Niklas, Strieder, Nicholas, Schmidl, Christian, Pant, Asmita, Gebhard, Claudia, Eigenberger, Andreas, Rehli, Michael, Prantl, Lukas, Hehlgans, Thomas, Brors, Benedikt, Imbusch, Charles D., Delacher, Michael, Feuerer, Markus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.08.2024
• Subjects: regulatory T cells; scATAC-seq; tissue adaptation; tissue-residing immune cells; transposable element; Treg cells; Treg cells; tissue adaptation; scATAC-seq; regulatory T cells; transposable element; tissue-residing immune cells
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2024.06.015

Tissue adaptation is required for regulatory T (Treg) cell function within organs. Whether this program shares aspects with other tissue-localized immune populations is unclear. Here, we analyzed single-cell chromatin accessibility data, including the transposable element (TE) landscape of CD45+ immune cells from colon, skin, adipose tissue, and spleen. We identified features of organ-specific tissue adaptation across different immune cells. Focusing on tissue Treg cells, we found conservation of the Treg tissue adaptation program in other tissue-localized immune cells, such as amphiregulin-producing T helper (Th)17 cells. Accessible TEs can act as regulatory elements, but their contribution to tissue adaptation is not understood. TE landscape analysis revealed an enrichment of specific transcription factor binding motifs in TE regions within accessible chromatin peaks. TEs, specifically from the LTR family, were located in enhancer regions and associated with tissue adaptation. These findings broaden our understanding of immune tissue residency and provide an important step toward organ-specific immune interventions. [Display omitted] •Generation of a scATAC-seq dataset of tissue-resident mouse and human immune cells•Tissue adaptation shows organ-specific and conserved features across immune cells•The tissue Treg cell adaptation program was conserved in AREG-producing Th17 cells•Families of accessible transposable elements are associated with tissue adaptation The general guidelines directing immune cell residency within tissues are poorly understood. Here, Simon et al. define the epigenetic landscapes and transposable element accessibility of CD45+ immune cells from murine and human tissues. This resource provides insights into organ-specific adaptation and shared and unique features of immune cell tissue residency.