Biology subjects

Bandeira, A.

Publications and source records attributed to Bandeira, A..

3 recordsLinked to original sources

bioRxiv2026

Embryonic lympho-epithelial cell interactions play an essential role in the establishment of adult T cell tolerance

Thymic seeding progenitors (TSP) colonize the embryonic thymus in two successive waves, with the first wave uniquely contributing to lymphoid tissue inducer and invariant {gamma}{delta} T cells that drive primordial medullary thymic epithelial cell (mTEC) maturation. Although recognized during thymic organogenesis, their long-term impact on T cell selection and immune tolerance remains unclear. We show that selective depletion of first-wave TSP alters thymic architecture and TEC composition. This results in reduced mTEC numbers, failure of medullary islets to expand and coalesce, altered dendritic cell composition, and delayed regulatory T cell development. Single-cell transcriptional analysis revealed a decrease in the most immature and expanding compartments and signs of accelerated maturation. It also revealed abnormal TEC differentiation trajectories, expansion of post-Aire and mimetic TEC subsets, and altered expression of tissue-restricted antigen-coding genes. Functionally, first-wave TSP depletion resulted in impaired thymic recovery after injury, and age-associated autoimmunity, with elevated anti-nuclear antibodies and lymphocytic infiltration in peripheral tissues. Thus, first-wave TSP imprint long-lasting control of thymic function and immune tolerance. One sentence summaryEarly embryonic thymic seeding progenitors program thymic epithelial maturation and regulatory T cell development, ensuring long-term immune tolerance and protection from age-associated autoimmunity.

immunology↗

bioRxiv2025

Distinct origin and fate for fetal hematopoietic progenitors

It was proposed that two sequential sources of intraembryonic multipotent progenitors ensure blood cell production from late gestation into adulthood, with only the latter producing self-renewing hematopoietic stem cells (HSC). How these two populations differ and how they impact the establishment of the postnatal immune system, remains poorly understood. Using complementary lineage tracing models, we showed that the first emerging embryonic multipotent progenitors (eMPP) are responsible for late gestation hematopoiesis. They are distinct from HSC that do not significantly contribute to embryonic mature blood cells. eMPP are the predominant source of embryonic lymphocytes and lymphoid tissue inducer cells, some of which persist for life. Between E12.5 and E16.5 eMPP rapidly differentiate, whereas HSC expand 20-fold. Altogether, these results support the notion that eMPP establish the embryonic adaptive immune system and shape the lymphoid organs where later adaptive immune responses occur, while HSC expand to sustain blood cell production throughout life.

developmental biology↗

bioRxiv2019

A wave of hematopoietic stem cell-derived T/ILC-restricted progenitors initiates thymopoiesis and shapes the embryonic thymus architecture.

Multiple waves of hematopoietic progenitors with distinct lineage potentials are differentially regulated in time and space. We show that the first thymic seeding progenitors comprise a unique population of bipotent cells that generate lymphoid tissue inducer and invariant V{gamma}5+ T cells. Both populations are of embryonic origin and induce the maturation of medullary thymic epithelial cells. Indeed, temporal depletion of the first wave of thymocytes results in a five-fold reduction of mature medullary thymic epithelial cells, after birth. We further show that these progenitors are of hematopoietic stem cell, and not, of yolk sac origin, despite the temporal overlap between the onset of lymphopoiesis and the transient expression of lymphoid transcripts in yolk sac precursors, that does not impact their strict erythro-myeloid potential. Our work highlights the relevance of the developmental timing on the emergence of different lymphoid subsets required for the establishment of a functionally diverse immune system.

immunology↗