Dynamics of thymus organogenesis and colonization in early human development

Development. 2013 May;140(9):2015-26. doi: 10.1242/dev.087320.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Carotid Arteries / embryology
  • Carotid Arteries / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Movement
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Embryonic Development
  • Endoderm / cytology
  • Endoderm / metabolism
  • Epithelium / embryology
  • Epithelium / metabolism
  • Female
  • Fetus / cytology
  • Fetus / embryology
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, SCID
  • Organogenesis*
  • PAX9 Transcription Factor / genetics
  • PAX9 Transcription Factor / metabolism
  • Pregnancy
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / embryology*
  • Thymus Gland / metabolism
  • Time Factors

Substances

  • Antigens, CD34
  • HOXA3 protein, human
  • Homeodomain Proteins
  • PAX9 Transcription Factor
  • PAX9 protein, human
  • T-Box Domain Proteins
  • TBX1 protein, human
  • Leukocyte Common Antigens
  • PTPRC protein, human