Adult zebrafish Langerhans cells arise from hematopoietic stem/progenitor cells

He, Sicong; Chen, J.; Jiang, Yunyun; Wu, Yi; Zhu, Lu; Wei, Jin; Zhao, Changlong; Yu, Tao; Wang, Tienan; Wu, Sung-Jung; Lin, Xi; Qu, Jianan Y.; Wen, Zilong; Zhang, Wenqing; Xu, Jin

doi:10.7554/elife.36131

Cited by 42 publications

(37 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenotype is reminiscent of that of Il34 mutant mice that selectively lack microglia and Langerhans cells (Greter et al, 2012; Wang et al, 2012). Previous studies claimed skin mpeg1 + hematopoietic branched cells in zebrafish to be Langerhans cells (He et al, 2018; Lin et al, 2019). It remains unclear whether these are true Langerhans cells, as there is no known zebrafish ortholog of langerin (CD207), the main marker of LCs in humans and mice.…”

Section: Discussionmentioning

confidence: 99%

“…We found that primitive myelopoiesis is initially csf1r -independent, although csf1r DM embryonic macrophages subsequently ceased to divide and failed to colonize embryonic tissues. Surprisingly, a detailed examination of csf1r DM larval zebrafish revealed another wave of mpeg1+ cells in the skin from 15-days of development onwards, but these cells lacked the branched morphology typical of Langerhans cells (He et al, 2018). Using fate mapping and gene expression profiling, we identified csf1r DM mpeg1+ cells as metaphocytes, a population of ectoderm-derived macrophage-like cells recently reported in zebrafish (Alemany et al, 2018a; Lin et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Kuil

Oosterhof

Ferrero

et al. 2020

Preprint

View full text Add to dashboard Cite

20Macrophages derive from multiple sources of hematopoietic progenitors. Most macrophages 21 require colony-stimulating factor 1 receptor (CSF1R), but some macrophages persist in the 22 absence of CSF1R. Here, we analyzed mpeg1:GFP-expressing macrophages in csf1r-23 deficient zebrafish and report that embryonic macrophages emerge followed by their 24 developmental arrest. In larvae, mpeg1+ cell numbers then increased showing two distinct 25 types in the skin: branched, putative Langerhans cells, and amoeboid cells. In contrast, 26 although numbers also increased in csf1r-mutants, exclusively amoeboid mpeg1+ cells were 27 present, which we showed by genetic lineage tracing to have a non-hematopoietic origin. 28They expressed macrophage-associated genes, but also showed decreased phagocytic 29 gene expression and increased epithelial-associated gene expression, characteristic of 30 metaphocytes, recently discovered ectoderm-derived cells. We further demonstrated that 31 juvenile csf1r-deficient zebrafish exhibit systemic macrophage depletion. Thus, Csf1r 32 deficiency disrupts embryonic to adult macrophage development. Csf1r-deficient zebrafish 33 are viable and permit analyzing the consequences of macrophage loss throughout life. 34 35 36 106 fate mapping and gene expression profiling, we identified csf1r DM mpeg1+ cells as 107 metaphocytes, a population of ectoderm-derived macrophage-like cells recently reported in 108 zebrafish (Alemany et al., 2018a; Lin et al., 2019). Extending our analyses, we further 109 demonstrated that adult csf1r DM fish exhibit a global defect in macrophage generation. In 110 5 conclusion, our study highlights distinct requirements for Csf1r during macrophage 111 generation and metaphocyte ontogeny, resolving part of the presumed macrophage 112 heterogeneity and their sensitivity to loss of Csf1r. 113 Results 114Zebrafish embryonic macrophages are formed independently of csf1r but display 115 migration and proliferation defects 207 both csf1r DM primitive macrophages and early microglia. 208Next, we assessed the presence of macrophages in developing csf1r DM animals by in 209 vivo fluorescence imaging of one lateral side of entire, individual larvae on 4 consecutive 210 days, starting at 5 dpf. We visualized ~450 macrophages in control animals, whereas csf1r DM 211 animals contained > 4-fold fewer (~100) ( Figure 3D). Over the next 4 days, macrophage 212 numbers in both groups remained stable ( Figure 3D). This suggests that, at this stage, there 213 is neither proliferative expansion of embryonic macrophages nor supply of macrophages 214 from an alternative source, causing macrophage numbers in csf1r DM larvae to remain much 215 lower than those in controls up to 9 dpf. Together these data indicate that, onwards from the 216 initiation of embryonic tissue colonization, proliferative expansion of macrophages remains 217 halted in csf1r DM animals.218 219 csf1r DM skin lacks highly branched putative Langerhans cells 220 8Given that macrophages are produced by consecutive waves of primiti...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Kuil

Oosterhof

Ferrero

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The sex of zebrafish embryos is difficult to confirm scientifically so the information is not provided. ABSR wild-type, Tg(Xla.Tubb:bcl-2) (Xu et al, 2016), Tg(hsp70:mCherry-T2a-CreER T2 ) (Hans et al, 2011), Tg(mpeg1:DsRedx) short for Tg(mpeg1:loxP-DsRedx-loxP-GFP) hkz15Tg (He et al, 2018), Tg(mpeg1:kaede) hkz16Tg , Tg(Xla.Tubb:csf1a) hkz17Tg , Tg(Xla.Tubb:csf1b) hkz18Tg , Tg(Xla.Tubb:il34) hkz19Tg , csf1ra j4e1 (Parichy et al, 2000), csf1a hkz9 , csf1b hkz10 , and il34 hkz11 are used in this study. All animal experiments were performed under approval from the Hong Kong University of Science and Technology's Animal Studies Committee.…”

Section: Star+methodsmentioning

confidence: 99%

Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors

et al. 2018

Self Cite

View full text Add to dashboard Cite

Microglia are the major immune cells in the central nervous system (CNS). Born in peripheral hematopoietic tissues, microglial precursors colonize the CNS during early embryogenesis and maintain themselves thereafter. However, the mechanism underlying this colonization process remains elusive. We have recently demonstrated that neuronal apoptosis contributes to microglia colonization in zebrafish. Here, we further show that prior to neuronal apoptosis, microglial precursors are attracted to the proximal brain regions by brain-derived interleukin 34 (il34) and its receptor colony-stimulating factor 1 receptor a (csf1ra). In both il34- and csf1ra-deficient zebrafish larva, embryonic macrophages fail to migrate to the anterior head and colonize the CNS, but their initial development and colonization to peripheral tissues remain largely unaffected. Activation of Il34-Csf1ra pathway is sufficient to attract embryonic macrophages to the CNS independent of neuronal apoptosis. Our study shows that cytokine signaling and neuronal apoptosis synergistically orchestrate the colonization of microglia in early zebrafish development.

show abstract

“…1a). Prior to this work, Kupffer cells were thought to be missing or sparse in zebrafish and other teleost species [31,32], but recent work tracing adult zebrafish Kupffer cells to their hematopoietic origin [33], and the data presented here collectively provide the first evidence for the prevalence of Kupffer cells in the zebrafish liver akin to their mammalian counterpart. Since the brain-LPS injection and subsequent analysis were conducted at 4 dpf, before the establishment of Kupffer cells, the presence of macrophages in the liver was likely because of active recruitment of peripheral macrophages and monocytes.…”

Section: Kupffer Cell Establishmentmentioning

confidence: 99%

Drainage of inflammatory macromolecules from brain to periphery targets the liver for macrophage infiltration

Jiménez

Earley

Hamlin

et al. 2020

Preprint

View full text Add to dashboard Cite

Many brain pathologies are associated with liver damage, but a direct link has long remained elusive. Here, we establish a new paradigm for interrogating brain-periphery interactions by leveraging zebrafish for its unparalleled access to the intact whole animal for in vivo analysis in real time after triggering focal brain inflammation. We reveal that drainage of inflammatory macromolecules from the brain led to a strikingly robust peripheral infiltration of macrophages into the liver independent of Kupffer cells. We further demonstrate that this macrophage recruitment requires signaling from the cytokine IL-34, Toll-like receptor adaptor protein MyD88, and neutrophils. These results highlight the ability for circulation of brain-derived substances to serve as a rapid mode of communication from brain to the liver. Understanding how the brain engages the periphery at times of danger may offer new perspectives for detecting and treating brain pathologies.

show abstract

Adult zebrafish Langerhans cells arise from hematopoietic stem/progenitor cells

Cited by 42 publications

References 79 publications

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Zebrafish macrophage developmental arrest underlies depletion of microglia and reveals Csf1r-independent metaphocytes

Il34-Csf1r Pathway Regulates the Migration and Colonization of Microglial Precursors

Drainage of inflammatory macromolecules from brain to periphery targets the liver for macrophage infiltration

Contact Info

Product

Resources

About