title: Dynamics of thymus organogenesis and colonization in early human development.
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.
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, CRM Building, 5 Little France Drive, Edinburgh..
authors.forename: Alison M
authors.initials: AM
authors.lastname: Farley
authors.forename: Lucy X
authors.initials: LX
authors.lastname: Morris
authors.forename: Eric
authors.initials: E
authors.lastname: Vroegindeweij
authors.forename: Marianne L G
authors.initials: ML
authors.lastname: Depreter
authors.forename: Harsh
authors.initials: H
authors.lastname: Vaidya
authors.forename: Frances H
authors.initials: FH
authors.lastname: Stenhouse
authors.forename: Simon R
authors.initials: SR
authors.lastname: Tomlinson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Tom
authors.initials: T
authors.lastname: Cupedo
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: C Clare
authors.initials: CC
authors.lastname: Blackburn
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D002339:Carotid Arteries / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D038081:Organogenesis; D051764:PAX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D018952:Antigens, CD34; C489832:HOXA3 protein, human; D018398:Homeodomain Proteins; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human