[Pubmed] Cross-species analyses of thymic mimetic cells reveal evolutionarily ancient origins and both conserved and spe

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Immunity. 2024 Dec 18:S1074-7613(24)00540-5. doi: 10.1016/j.immuni.2024.11.025. Online ahead of print.

ABSTRACT

Thymic mimetic cells are molecular hybrids between medullary-thymic-epithelial cells (mTECs) and diverse peripheral cell types. They are involved in eliminating autoreactive T cells and can perform supplementary functions reflective of their peripheral-cell counterparts. Current knowledge about mimetic cells derives largely from mouse models. To provide the high resolution that proved revelatory for mice, we performed single-cell RNA sequencing on purified mimetic-cell compartments from human pediatric donors. The single-cell profiles of individual donors were surprisingly similar, with diversification of neuroendocrine subtypes and expansion of the muscle subtype relative to mice. Informatic and imaging studies on the muscle-mTEC population highlighted a maturation trajectory suggestive of skeletal-muscle differentiation, some striated structures, and occasional cellular groupings reminiscent of neuromuscular junctions. We also profiled thymic mimetic cells from zebrafish. Integration of data from the three species identified species-specific adaptations but substantial interspecies conservation, highlighting the evolutionarily ancient nature of mimetic mTECs. Our findings provide a landscape view of human mimetic cells, with anticipated relevance in autoimmunity.

PMID:39731911 | DOI:10.1016/j.immuni.2024.11.025


Source: https://pubmed.ncbi.nlm.nih.gov/3973191 ... t9+e462414