754 results match your criteria thymopoiesis

Development of double-positive thymocytes at single-cell resolution.

Genome Med 2021 Mar 26;13(1):49. Epub 2021 Mar 26.

Department of oncology, The First Affiliated Hospital of USTC, Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, School of Basic Medicine, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230021, Anhui, China.

Background: T cells generated from thymopoiesis are essential for the immune system, and recent single-cell studies have contributed to our understanding of the development of thymocytes at the genetic and epigenetic levels. However, the development of double-positive (DP) T cells, which comprise the majority of thymocytes, has not been well investigated.

Methods: We applied single-cell sequencing to mouse thymocytes and analyzed the transcriptome data using Seurat. Read More

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Cell competition in hematopoietic cells: Quality control in homeostasis and its role in leukemia.

Dev Biol 2021 Feb 27;475:1-9. Epub 2021 Feb 27.

Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ciência, Calouste Gulbenkian Foundation, Oeiras, 2780-156, Portugal. Electronic address:

Cell competition contributes to optimal organ function by promoting tissue homogeneity. In the hematopoietic system, cell competition has been described in two distinct cell populations: in hematopoietic stem cells, and in differentiating T lymphocytes, or thymocytes. In hematopoietic stem cells, cell competition was studied in the context of mild irradiation, whereby the levels of p53 determined the outcome of the cellular interactions and the cells with lower p53 were in advantage. Read More

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February 2021

Thymopoiesis, Alterations in Dendritic Cells and Tregs, and Reduced T Cell Activation in Successful Extracorporeal Photopheresis Treatment of GVHD.

J Clin Immunol 2021 Mar 2. Epub 2021 Mar 2.

Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.

Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplant (HSCT) and negatively affects T cell reconstitution. Extracorporeal photopheresis (ECP) reduces aGVHD, but the mechanisms remain incompletely understood. Our objective was to examine the impact of ECP on thymopoiesis in pediatric aGVHD and the mechanisms at a cellular and transcriptional level. Read More

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α1-Antitrypsin Causing CD8 Downregulation during Thymocyte Differentiation.

Trends Immunol 2021 Mar 2;42(3):177-178. Epub 2021 Feb 2.

Institute for Human Genetics and Biochemistry, Vesenaz, Switzerland.

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Thymic activity in immune recovery after allogeneic hematopoietic stem cell transplantation in children.

Cent Eur J Immunol 2020 26;45(2):151-159. Epub 2020 Feb 26.

Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, Poland.

Thymic output was studied prospectively in 52 children who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thymic activity was assessed by quantification of recent thymic emigrants (RTE) discriminated from the rest of naive T cells by immunophenotype CD3+/CD4+/CD31+/CD45RA+. Thymic output was analyzed in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence thymopoiesis: underlying disease, type of HSCT, source of stem cells, age of recipient and donor, type of conditioning, implemented graft versus host disease (GvHD) prophylaxis, viral reactivations (herpes viruses cytomegalovirus - CMV, Epstein-Barr virus - EBV, adenovirus - ADV, BK virus - BKV), occurrence and grade of both acute and chronic graft versus host disease (aGvHD, cGvHD) and number of transplanted CD34 cells/kg. Read More

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February 2020

T cell development in a dish.

Nat Methods 2021 01;18(1):35

Nature Methods, .

Artificial thymic organoid systems recapitulate murine thymopoiesis in vitro. Read More

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January 2021

Corrigendum: Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development.

Front Immunol 2020 30;11:628464. Epub 2020 Nov 30.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

[This corrects the article DOI: 10.3389/fimmu.2019. Read More

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November 2020

Inborn errors of thymic stromal cell development and function.

Semin Immunopathol 2021 Feb 30;43(1):85-100. Epub 2020 Nov 30.

Developmental Immunology, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

As the primary site for T cell development, the thymus is responsible for the production and selection of a functional, yet self-tolerant T cell repertoire. This critically depends on thymic stromal cells, derived from the pharyngeal apparatus during embryogenesis. Thymic epithelial cells, mesenchymal and vascular elements together form the unique and highly specialised microenvironment required to support all aspects of thymopoiesis and T cell central tolerance induction. Read More

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February 2021

Retracing the evolutionary emergence of thymopoiesis.

Sci Adv 2020 Nov 27;6(48). Epub 2020 Nov 27.

Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.

The onset of lymphocyte development in the vertebrate primordial thymus, about 500 million years ago, represents one of the foundational events of the emerging adaptive immune system. Here, we retrace the evolutionary trajectory of thymopoiesis, from early vertebrates to mammals, guided by members of the transcription factor gene family, which direct the differentiation of the thymic microenvironment. Molecular engineering in transgenic mice recapitulated a gene duplication event, exon replacements, and altered expression patterns. Read More

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November 2020

In Vitro Recapitulation of Murine Thymopoiesis from Single Hematopoietic Stem Cells.

Cell Rep 2020 10;33(4):108320

Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA; Division of Pediatric Hematology-Oncology, Department of Pediatrics, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. Electronic address:

We report a serum-free, 3D murine artificial thymic organoid (M-ATO) system that mimics normal murine thymopoiesis with the production of all T cell stages, from early thymic progenitors to functional single-positive (CD8SP and CD4SP) TCRαβ and TCRγδ cells. RNA sequencing aligns M-ATO-derived populations with phenotypically identical primary thymocytes. M-ATOs initiated with Rag1 marrow produce the same differentiation block as seen in the endogenous thymus, and Notch signaling patterns in M-ATOs mirror primary thymopoiesis. Read More

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October 2020

Processing Human Thymic Tissue for Single Cell RNA-Seq.

STAR Protoc 2020 Sep 24;1(2):100090. Epub 2020 Aug 24.

Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

Single cell RNA sequencing of human thymic cells is dependent on isolation of highly pure and viable cell populations. This protocol describes the isolation of CD34 progenitor and more differentiated CD34 fractions from post-natal thymic tissue to study thymopoiesis. CD34 cells represent <1% of thymic cells, so this protocol uses magnetic- followed by fluorescence-activated cell separation to isolate highly enriched CD34 cells. Read More

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September 2020

The contribution of thymic tolerance to central nervous system autoimmunity.

Semin Immunopathol 2021 Feb 27;43(1):135-157. Epub 2020 Oct 27.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.

Autoimmune diseases of the central nervous system (CNS) are associated with high levels of morbidity and economic cost. Research efforts have previously focused on the contribution of the peripheral adaptive and innate immune systems to CNS autoimmunity. However, a failure of thymic negative selection is a necessary step in CNS-reactive T cells escaping into the periphery. Read More

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February 2021

UM171-Expanded Cord Blood Transplants Support Robust T Cell Reconstitution with Low Rates of Severe Infections.

Transplant Cell Ther 2021 Jan 3;27(1):76.e1-76.e9. Epub 2020 Oct 3.

Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada; Division of Hematology-Oncology, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada. Electronic address:

Rapid T cell reconstitution following hematopoietic stem cell transplantation (HSCT) is essential for protection against infections and has been associated with lower incidence of chronic graft-versus-host disease (cGVHD), relapse, and transplant-related mortality (TRM). While cord blood (CB) transplants are associated with lower rates of cGVHD and relapse, their low stem cell content results in slower immune reconstitution and higher risk of graft failure, severe infections, and TRM. Recently, results of a phase I/II trial revealed that single UM171-expanded CB transplant allowed the use of smaller CB units without compromising engraftment (www. Read More

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January 2021

Possible Role of the Gene in Primary and Secondary Lymphedema: Review of the Literature and Genetic Study of Two Rare Causative Variants.

Lymphat Res Biol 2020 Sep 22. Epub 2020 Sep 22.

MAGI Euregio, Bolzano, Italy.

RAR-related Orphan Receptor C (RORC) is a DNA-binding transcription factor and the key transcription factor responsible for differentiation of T helper 17 cells. The gene plays a role in lymphoid organogenesis, thymopoiesis, and lymph node organogenesis. The aim of our study was to determine the possible role of in the development of lymphatic system malformations by combining data from the scientific literature and next-generation sequencing of in lymphedema patients negative for known causative genes. Read More

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September 2020

Augmented autophagy suppresses thymocytes development via Bcl10/p-p65 pathway in prenatal nicotine exposed fetal mice.

Ecotoxicol Environ Saf 2021 Jan 11;207:111272. Epub 2020 Sep 11.

Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China. Electronic address:

Tobacco smoke is a common global environmental pollutant. Maternal tobacco smoke/nicotine exposure has long-term toxic effects on immune organs. We previously found that prenatal nicotine exposure (PNE)-induced programmed immune diseases caused by fetal thymic hypoplasia, but the mechanism still unknown. Read More

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January 2021

Conventional and Computational Flow Cytometry Analyses Reveal Sustained Human Intrathymic T Cell Development From Birth Until Puberty.

Front Immunol 2020 4;11:1659. Epub 2020 Aug 4.

Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

The thymus is the organ where subsets of mature T cells are generated which subsequently egress to function as central mediators in the immune system. While continuously generating T cells even into adulthood, the thymus does undergo involution during life. This is characterized by an initial rapid decrease in thymic cellularity during early life and by a second age-dependent decline in adulthood. Read More

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Evaluating Thymic Function After Human Hematopoietic Stem Cell Transplantation in the Personalized Medicine Era.

Front Immunol 2020 31;11:1341. Epub 2020 Jul 31.

Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment option for several malignant and non-malignant hematological diseases. The clinical outcome of this procedure relies to a large extent on optimal recovery of adaptive immunity. In this regard, the thymus plays a central role as the primary site for generation of functional, diverse, and immunocompetent T-lymphocytes. Read More

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Thymic rejuvenation via FOXN1-reprogrammed embryonic fibroblasts (FREFs) to counteract age-related inflammation.

JCI Insight 2020 09 17;5(18). Epub 2020 Sep 17.

Age-associated systemic, chronic inflammation is partially attributed to increased self-autoreactivity, resulting from disruption of central tolerance in the aged, involuted thymus. This involution causally results from gradually decreased expression of the transcription factor FOXN1 in thymic epithelial cells (TECs), whereas exogenous FOXN1 in TECs can partially rescue age-related thymic involution. TECs induced from FOXN1-overexpressing embryonic fibroblasts can generate an ectopic de novo thymus under the kidney capsule, and intrathymic injection of naturally young TECs can lead to middle-aged thymus regrowth. Read More

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September 2020

Androgen Receptors in Epithelial Cells Regulate Thymopoiesis and Recent Thymic Emigrants in Male Mice.

Front Immunol 2020 29;11:1342. Epub 2020 Jun 29.

Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.

Androgens have profound effects on T cell homeostasis, including regulation of thymic T lymphopoiesis (thymopoiesis) and production of recent thymic emigrants (RTEs), i. e., immature T cells that derive from the thymus and continue their maturation to mature naïve T cells in secondary lymphoid organs. Read More

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Cell Competition, the Kinetics of Thymopoiesis, and Thymus Cellularity Are Regulated by Double-Negative 2 to 3 Early Thymocytes.

Cell Rep 2020 07;32(3):107910

Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ciência, Calouste Gulbenkian Foundation, Oeiras 2780-156, Portugal. Electronic address:

Cell competition in the thymus is a homeostatic process that drives turnover. If the process is impaired, thymopoiesis can be autonomously maintained for several weeks, but this causes leukemia. We aimed to understand the effect of cell competition on thymopoiesis, identify the cells involved, and determine how the process is regulated. Read More

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Development and characterization of novel mouse monoclonal antibodies against chicken chemokine CC motif ligand 4.

Vet Immunol Immunopathol 2020 Sep 10;227:110091. Epub 2020 Jul 10.

Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture Beltsville, MD, 20705, USA. Electronic address:

Chemokine (C-C motif) ligand (CCL) 4 is a CC chemokine subfamily member defined by the sequential positioning of conserved cysteine residues. Upon the binding of G-protein-coupled receptors on the cell surface, CCL4 mediates a diverse set of biological processes including chemotaxis, tumorigenesis, homeostasis and thymopoiesis. Although the physiological roles of mammalian CCL4s were elucidated >20 years ago, there is limited information on the biological activities of chicken CCL4 (chCCL4). Read More

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September 2020

Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation.

J Exp Med 2020 09;217(9)

Université de Paris (Descartes), Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris, Hôpital Necker Enfants-Malades, Paris, France.

Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Read More

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September 2020

Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning.

Int J Mol Med 2020 Sep 24;46(3):1166-1174. Epub 2020 Jun 24.

Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.

Bone marrow (BM) transplantation (BMT) represents a curative treatment for various hematological disorders. Prior to BMT, a large amount of the relevant anticancer drug needed to be administered to eliminate cancer cells. However, during this pre‑BMT cytotoxic conditioning regimen, hematopoietic stem cells in the BM and thymic epithelial cells were also destroyed. Read More

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September 2020

Single-Cell RNA-Seq Mapping of Human Thymopoiesis Reveals Lineage Specification Trajectories and a Commitment Spectrum in T Cell Development.

Immunity 2020 06;52(6):1105-1118.e9

Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address:

The challenges in recapitulating in vivo human T cell development in laboratory models have posed a barrier to understanding human thymopoiesis. Here, we used single-cell RNA sequencing (sRNA-seq) to interrogate the rare CD34 progenitor and the more differentiated CD34 fractions in the human postnatal thymus. CD34 thymic progenitors were comprised of a spectrum of specification and commitment states characterized by multilineage priming followed by gradual T cell commitment. Read More

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Reply: Thymopoiesis, inflamm-aging, and COVID-19 phenotype.

Chih-Jung Chen

Pediatr Neonatol 2020 06 21;61(3):366-367. Epub 2020 Apr 21.

Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, 333, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, 333, Taoyuan, Taiwan. Electronic address:

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Role of thymopoiesis and inflamm-aging in COVID-19 phenotype.

Pediatr Neonatol 2020 06 15;61(3):364-365. Epub 2020 Apr 15.

Rheumatology Research Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, via S. Pansini 5, 80131, Naples, Italy.

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Integrated scRNA-Seq Identifies Human Postnatal Thymus Seeding Progenitors and Regulatory Dynamics of Differentiating Immature Thymocytes.

Immunity 2020 06 17;52(6):1088-1104.e6. Epub 2020 Apr 17.

Faculty of Medicine and Health Sciences, Department of Diagnostic Sciences, Ghent University, C. Heymanslaan 10, MRB2, Entrance 38, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium. Electronic address:

During postnatal life, thymopoiesis depends on the continuous colonization of the thymus by bone-marrow-derived hematopoietic progenitors that migrate through the bloodstream. The current understanding of the nature of thymic immigrants is largely based on data from pre-clinical models. Here, we employed single-cell RNA sequencing (scRNA-seq) to examine the immature postnatal thymocyte population in humans. Read More

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Frailty, markers of immune activation and oxidative stress in HIV infected elderly.

PLoS One 2020 18;15(3):e0230339. Epub 2020 Mar 18.

Laboratorio Inmuno-Biología Molecular (LIBM), Immunology Section, Hospital General Universitario Gregorio Marañón, Madrid, Spain.

People living with HIV-1 experience an accelerated aging due to the persistent and chronic activation of the immune system. This phenomenon conduces to immune exhaustion and precipitate immunosenescence. In general, frailty is defined as a syndrome of physiological degeneration in the elderly. Read More

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Thymic Epithelial Cells Contribute to Thymopoiesis and T Cell Development.

Front Immunol 2019 31;10:3099. Epub 2020 Jan 31.

Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

The thymus is the primary lymphoid organ responsible for the generation and maturation of T cells. Thymic epithelial cells (TECs) account for the majority of thymic stromal components. They are further divided into cortical and medullary TECs based on their localization within the thymus and are involved in positive and negative selection, respectively. Read More

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November 2020