| Title: |
Combinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development |
| Authors: |
Provin, Nathan; D’arco, Manon; Le Bozec, Antoine; Kervagoret, Erwan; Bruneau, Alexandre; Brusselle, Lucas; Fourgeux, Cynthia; Poschmann, Jeremie; Hulin, Philippe; Maminirina, Pierre; Baron, Olivier; Saulquin, Xavier; Guillonneau, Carole; David, Laurent; Giraud, Matthieu |
| Contributors: |
Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI); Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ); Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine (Team 2 - U1064 Inserm - CR2TI); Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE); Team 6 : Impact of acute inflammation on host pathogen interactions and lung homeostasis (Team 6 - U1064 Inserm - CR2TI); Plateforme MicroPicell Nantes; Université de Nantes (UN); Structure fédérative de recherche François Bonamy (Nantes Univ - SFR François Bonamy); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - pôle Santé; BioCore Nantes; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Nantes Université (Nantes Univ); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Bordeaux sciences économiques (BSE); Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1); Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA); Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE); Université de Nantes (UN)-Université de Nantes (UN); Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST); Nantes Université - pôle Sciences et technologie; 22001/National Organization for Rare Disorders (National Organization for Rare Disorders, Inc.); ANR-19-RAR4-0011,TARID,Thymic Abnormalities in Rare Immunological Diseases(2019) |
| Source: |
ISSN: 2041-1723. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2026 |
| Collection: |
Université de Nantes: HAL-UNIV-NANTES |
| Subject Terms: |
MESH: CD4-Positive T-Lymphocytes* / cytology; MESH: CD8-Positive T-Lymphocytes* / cytology; MESH: Induced Pluripotent Stem Cells* / cytology; MESH: Induced Pluripotent Stem Cells* / metabolism; MESH: Organoids / cytology; MESH: Thymus Gland* / cytology; MESH: Cell Differentiation; MESH: Cell Lineage; MESH: Cells; Cultured; MESH: Coculture Techniques; MESH: Dendritic Cells* / cytology; MESH: Epithelial Cells / cytology; MESH: Epithelium / metabolism; MESH: Humans; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; The thymus educates thymocytes through a selection process mediated by thymic epithelial cells (TECs). Recent advances have made the generation of T lymphocytes from induced pluripotent stem cells (iPSc) a promising therapeutic strategy. However, current approaches often fail to replicate the thymic niche, leading to impaired T cell generation. Here we address the production of functional mature iPSc-derived TECs supporting in vitro T cell generation. We optimize thymic lineage differentiation through an unbiased multifactorial experimental design. By modulating specific signaling pathways, we generate progenitors that mature into medullary and cortical TECs. Co-culture with primary hematopoietic progenitors in a 3D thymic organoid setup induces their differentiation into CD4 + and CD8 + T cells. Importantly, thymic organoids support multilineage differentiation, with dendritic cell populations also emerging. Thus, the presented thymic organoid model provides a practical platform for studying thymic cellular interactions and thymopoiesis in vitro, and opens further research perspectives towards cell-based therapies. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/41577697; PUBMED: 41577697; PUBMEDCENTRAL: PMC12932823; WOS: 001699326900016 |
| DOI: |
10.1038/s41467-026-68675-y |
| Availability: |
https://inserm.hal.science/inserm-05561026; https://inserm.hal.science/inserm-05561026v1/document; https://inserm.hal.science/inserm-05561026v1/file/s41467-026-68675-y.pdf; https://doi.org/10.1038/s41467-026-68675-y |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.9CCDE6A5 |
| Database: |
BASE |