Adult zebrafish Langerhans cells arise from hematopoietic stem/progenitor cells

Elife. 2018 Jun 15;7:e36131. doi: 10.7554/eLife.36131.


The origin of Langerhans cells (LCs), which are skin epidermis-resident macrophages, remains unclear. Current lineage tracing of LCs largely relies on the promoter-Cre-LoxP system, which often gives rise to contradictory conclusions with different promoters. Thus, reinvestigation with an improved tracing method is necessary. Here, using a laser-mediated temporal-spatial resolved cell labeling method, we demonstrated that most adult LCs originated from the ventral wall of the dorsal aorta (VDA), an equivalent to the mouse aorta, gonads, and mesonephros (AGM), where both hematopoietic stem cells (HSCs) and non-HSC progenitors are generated. Further fine-fate mapping analysis revealed that the appearance of LCs in adult zebrafish was correlated with the development of HSCs, but not T cell progenitors. Finally, we showed that the appearance of tissue-resident macrophages in the brain, liver, heart, and gut of adult zebrafish was also correlated with HSCs. Thus, the results of our study challenged the EMP-origin theory for LCs.

Keywords: Langerhans cell; developmental biology; lineage tracing; regenerative medicine; stem cells; tissue resident macrophage; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Aorta / cytology
  • Aorta / embryology
  • Aorta / growth & development
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology*
  • Gonads / cytology
  • Gonads / embryology
  • Gonads / growth & development
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Langerhans Cells / cytology
  • Langerhans Cells / physiology*
  • Macrophages / metabolism
  • Mesonephros / cytology
  • Mesonephros / embryology
  • Mesonephros / growth & development
  • Mice
  • Microscopy, Confocal
  • Zebrafish


  • Green Fluorescent Proteins

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.