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Dynamics of thymus organogenesis and colonization in early human development.

TitleDynamics of thymus organogenesis and colonization in early human development.
Publication TypeJournal Article
Year of Publication2013
AuthorsFarley A, Morris LX, Vroegindeweij E, Depreter MGL, Vaidya HJayesh, Stenhouse FH, Tomlinson SR, Anderson RA, Cupedo T, Cornelissen JJ, C Blackburn C
JournalDevelopment
Volume140
Issue9
Pagination2015-26
Date Published2013 May
ISSN1477-9129
KeywordsAnimals, Antigens, CD34, Antigens, CD45, Carotid Arteries, Cell Differentiation, Cell Lineage, Cell Movement, Embryo, Mammalian, Embryonic Development, Endoderm, Epithelium, Female, Fetus, Gene Expression Regulation, Developmental, Homeodomain Proteins, Humans, Immunohistochemistry, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Organogenesis, PAX9 Transcription Factor, Pregnancy, T-Box Domain Proteins, Thymus Gland, Time Factors
Abstract

The thymus is the central site of T-cell development and thus is of fundamental importance to the immune system, but little information exists regarding molecular regulation of thymus development in humans. Here we demonstrate, via spatial and temporal expression analyses, that the genetic mechanisms known to regulate mouse thymus organogenesis are conserved in humans. In addition, we provide molecular evidence that the human thymic epithelium derives solely from the third pharyngeal pouch, as in the mouse, in contrast to previous suggestions. Finally, we define the timing of onset of hematopoietic cell colonization and epithelial cell differentiation in the human thymic primordium, showing, unexpectedly, that the first colonizing hematopoietic cells are CD45(+)CD34(int/-). Collectively, our data provide essential information for translation of principles established in the mouse to the human, and are of particular relevance to development of improved strategies for enhancing immune reconstitution in patients.

DOI10.1242/dev.087320
Alternate JournalDevelopment
PubMed ID23571219
PubMed Central IDPMC3631974
Grant ListG1100357 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom