Sex-biased human thymic architecture guides T cell development through spatially defined niches
Within the thymus, regulation of the cellular crosstalk directing T cell development depends on spatial interactions within specialized niches. To create a spatially defined map of tissue niches guiding human postnatal T cell development, we employed the multidimensional imaging platform co-detection by indexing (CODEX) as well as cellular indexing of transcriptomes and epitopes sequencing (CITE-seq) and assay for transposase accessible chromatin sequencing (ATAC-seq). We generated age-matched 4- to 5-month-old human postnatal thymus datasets for male and female donors, identifying significant sex differences in both T cell and thymus biology. We demonstrate a possible role for JAG ligands in directing thymic-like dendritic cell development, identify important functions of a population of extracellular matrix (ECM)<sup>-</sup> fibroblasts, and characterize the medullary niches surrounding Hassall's corpuscles. Together, these data represent an age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, providing an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.
Authors
- Megan K. Levings (ORCID: https://orcid.org/0000-0002-0305-5790)
- Elizabeth J. Rideout (ORCID: https://orcid.org/0000-0003-0012-2828)
- Kevin Salim (ORCID: https://orcid.org/0000-0003-3793-0415)
- Ross D. Jones (ORCID: https://orcid.org/0000-0003-0891-6761)
- Peter W. Zandstra (ORCID: https://orcid.org/0000-0002-9568-733X)
- John M. Edgar (ORCID: https://orcid.org/0000-0001-5678-6485)
- Lauren J. Durland (ORCID: https://orcid.org/0000-0001-5740-8670)
- Matthew C. Major
- Fábio Rossi (ORCID: https://orcid.org/0000-0002-0368-2620)
- Yu Xin Wang (ORCID: https://orcid.org/0000-0001-8440-9388)
- Laura N Stankiewicz (ORCID: https://orcid.org/0000-0002-3982-5558)
- Grace C. Bingham (ORCID: https://orcid.org/0000-0002-5223-0460)
- Helen M. Blau (ORCID: https://orcid.org/0000-0001-6503-5480)
- Emily A Flaschner
- Bruce Z B Lin
Institutions
- University of British Columbia Hospital (CA)
- University of British Columbia (CA)
- Discovery Institute (US)
- BC Children's Hospital (CA)
- University of Virginia (US)
- Stanford University (US)
- Baxter (United States) (US)
Publication Details
- Journal
- Developmental Cell
- Published
- 2024-10-08
- DOI
- https://doi.org/10.1016/j.devcel.2024.09.011
- Citations
- 20
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 4.57
Funders
- Li Ka Shing Foundation
- BC Children's Hospital
- Universities Space Research Association
- Michael Smith Health Research BC
- Genome British Columbia
- National Institutes of Health
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- British Columbia Knowledge Development Fund