Adult zebrafish Langerhans cells arise from hematopoietic stem/progenitor cells
Abstract
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.
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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all figures and supplementary figures.
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Funding
National Natural Science Foundation of China (31229003)
- Zilong Wen
Research Grants Council, University Grants Committee (16102414)
- Zilong Wen
Innovation and Technology Commission (ITCPD/17-9)
- Zilong Wen
Research Grants Council, University Grants Committee (16103515)
- Zilong Wen
Research Grants Council, University Grants Committee (HKUST5/CRF/12R)
- Zilong Wen
Research Grants Council, University Grants Committee (AoE/M-09/12)
- Zilong Wen
Research Grants Council, University Grants Committee (T13-607/12R)
- Zilong Wen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, He et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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