The functional relationship between hematopoietic stem cells and developing T lymphocytes

• Published in: Annals of the New York Academy of Sciences Vol. 1370; no. 1; pp. 36 - 44
• Main Authors: Staal, Frank J.T., Wiekmeijer, Anna-Sophia, Brugman, Martijn H., Pike-Overzet, Karin
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.04.2016; Wiley Subscription Services, Inc
• Subjects: Animals; barcoding; Bone marrow; Cell Differentiation - immunology; Cell Lineage - immunology; hematopoietic stem cell; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Humans; Lymphocytes; Mice; Rodents; SCID; Stem cells; T cell; T-Lymphocytes - cytology; T-Lymphocytes - immunology; thymus; Thymus Gland - cytology; Thymus Gland - immunology; barcoding; hematopoietic stem cell; thymus; SCID; T cell
• ISSN: 0077-8923; 1749-6632; 1749-6632
• DOI: 10.1111/nyas.12995

In contrast to all other blood and immune cells, T lymphocytes do not develop in the bone marrow (BM), but in the specialized microenvironment provided by the thymus. Similar to the other lineages, however, all T cells arise from multipotent hematopoietic stem cells (HSCs) that reside in the BM. Not all HSCs give rise to T cells; but how many and what kind of developmental checkpoints are located along this intricate differentiation path is the subject of intense research. Traditionally, this process has been studied almost exclusively using mouse cells, but recent advances in immunodeficient mouse models, high‐speed cell sorting, lentiviral transduction protocols, and deep sequencing techniques have allowed these questions to be addressed using human cells. Here we review the process of thymic seeding by BM‐derived cells and T cell commitment in humans, discussing recent insights into the clonal composition of the thymus and the definition of developmental checkpoints, on the basis of insights from human severe combined immunodeficiency patients.