Project description:The single cell and bulk expression profiles of early pro T-cell progenitors generated from purified mouse bone marrow, cultured on different stromal cell systems
Project description:Although the advent of organoids opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here we established organoids from the thymus, the lymphoid organ responsible for T cell development. We identified conditions enabling thymic epithelial progenitor cell proliferation and development into organoids with diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. Contrary to these two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T cell development upon reaggregation with T cell progenitors. The reaggregates showed in vivo-like epithelial diversity and ability to attract T cell progenitors. Thymic epithelial organoids are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries.
Project description:Gene expression analysis of early thymic progenitors and thymus seeding progenitors Eight distinct populations were analysed, each with between 2 and 6 biological replicates.
Project description:Purpose: The goal of this study is to characterise cortical (cTECs) and medullary (mTECs) epithelial cells of the human thymus. Methods: FACS-isolation protocol to separate 4 different epithelial cells populations from total dissociation of human thymus that is negative for hCD45 and either positive for EPCAM or CD205, then loaded into the 10x Genomics Chromium Platform, and sequenced using Illumina HiSeq 4000. Conclusions: Our study identified and characterised human thymic stem/progenitors cells, as well as identified new specialised cell clusters in each of the two compartments
Project description:Human T lymphogenesis includes emergence, migration and thymus-seeding of T lymphoid precursor, followed by T-lymphocytes commitment in thymus, which are largely unknown. Here, we perform single-cell RNA sequencing using cells isolated from human hemogenic/hematopoietic sites such as aorto-gonad-mesonephros (AGM), liver, and thymic primordia spanning embryonic and fetal stages. The transcriptional atlas of thymic primordia illustrates the cellular trajectory of early T-lymphocyte development. Further, thymic seeding progenitors in liver and unique T lymphoid progenitors in AGM at CS14, are first unveiled. We also reveal the stepwise-specification of thymic epithelial cells,and the potential cell-cell interactions between T-lymphocyte progenitors and stromal cells during thymus organogenesis. Our data provide new insights into T lymphogenesis, which prospectively directs the efficient regeneration of T- lymphocytes from pluripotent stem cells
Project description:The purpose of this bulk RNA-seq experiment is to identify candidate genes that can mark proliferating isthmus progenitors in the mouse stomach corpus epithelium. The cycling isthmus progenitors were isolated based on mVenus expression in FUCCI mouse and used for bulk RNA-seq data generation. The corpus epithelium was stained with E-cadherin and E-cadherin+ cells were also sorted and used for the control.