Qualitative Changes in Cortical Thymic Epithelial Cells Drive Postpartum Thymic Regeneration

Abstract

During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition.,

Publication
Frontiers in Immunology
Tariq Daouda
Tariq Daouda
Étudiant au doctorat en bio-informatique (2011-2018 avec Claude Perrault, IRIC)
Jérémie Zumer
Jérémie Zumer
PhD student in Computer Science

Doctoral student in Computer Science | Improving peptide mass spectrometry using deep learning

Sébastien Lemieux
Sébastien Lemieux
Principal Investigator

Principal Investigator, Functional and Structural Bioinformatics Research Unit, IRIC | Scientific direction of the Bioinformatics platform | Associate Professor, Department of Biochemistry and Molecular Medicine, Université de Montréal