Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish

Xu, Jin; Zhu, Lu; He, Sicong; Wu, Yi; Wei, Jin; Yu, Tao; Qu, Jianan Y.; Wen, Zilong

doi:10.1016/j.devcel.2015.08.018

Cited by 151 publications

(181 citation statements)

References 65 publications

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“…2d). To more specifically label individual HSPCs, we adapted an hsp70l laser induction method that was used to trace microglial precursors in zebrafish 15 . At 48 hpf, there are only 10–15 cd41:eGFP + cells along the VDA 1,16 .…”

Section: Resultsmentioning

confidence: 99%

Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development

et al. 2016

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Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creERT2 in developing cd41:eGFP+ HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drl:creERT2 that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny. Our findings reveal that approximately 21 HSC clones exist prior to HSC emergence and 30 clones are present during peak production from aortic endothelium. Our methods further reveal that stress haematopoiesis, including sublethal irradiation and transplantation, reduces clonal diversity. Our findings provide quantitative insights into the early clonal events that regulate haematopoietic development.

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Section: Resultsmentioning

confidence: 99%

Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development

et al. 2016

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“…However, later studies challenged this single source viewpoint by using temporal-spatial resolution fate mapping [48]. This study indicated that two different origins of microglia could be identified in zebrafish.…”

Section: Microglia Origins: From the Yolk Sac Or Non-yolk Sac Sources?mentioning

confidence: 99%

An updated assessment of microglia depletion: current concepts and future directions

2017

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Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris. It is now well accepted that the dysfunction of microglia and microglia-induced neuroinflammation are implicated in the occurrence and progression of many neurological diseases. Although the past decade has witnessed major progress in understanding of multi-tasking microglia, what remains largely enigmatic is the relative importance of microglia at different disease stages and how microglia should be targeted for optimal therapeutic efficacy. Notably, microglia depletion through genetic targeting or pharmacological therapies can be viewed as effective tools to stimulate new microglia to repopulate the central nervous system. Microglia depletion and subsequent repopulation at defined stages in various experimental animal model disorders allow us to extend our knowledge of molecular mechanisms, thus holding promise for designing strategies to resolve neuroinflammation and promote recovery. Herein we highlight the highly plastic and diverse phenotypes of microglia and outline the lessons learned from microglia depletion approaches.

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“…This process of sequential colonization of tissues by macrophages has also been observed during zebrafish development. However, in zebrafish, the brain continues to be colonized by new macrophages, resulting in the replacement of embryonic-derived microglia with adult-derived microglia [68]. In all other tissues examined in the murine embryo, macrophages derived from primitive hematopoiesis are replaced, or diluted, by macrophages derived from EMPs, or eventually, HSCs.…”

Section: Source Of Tissue-resident Macrophage Populations In the Fmentioning

confidence: 99%

Early hematopoiesis and macrophage development

McGrath

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Palis

2015

Seminars in Immunology

145

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The paradigm that all blood cells are derived from hematopoietic stem cells (HSCs) has been challenged by two findings. First, there are tissue-resident hematopoietic cells, including subsets of macrophages that are not replenished by adult HSCs, but instead are maintained by self-renewal of fetal-derived cells. Second, during embryogenesis, there is a conserved program of HSC-independent hematopoiesis that precedes HSC function and is required for embryonic survival. The presence of waves of HSC-independent hematopoiesis as well as fetal HSCs raises questions about the origin of fetal-derived adult tissue-resident macrophages. In the murine embryo, historical examination of embryonic macrophage and monocyte populations combined with recent reports utilizing genetic lineage-tracing approaches has led to a model of macrophage ontogeny that can be integrated with existing models of hematopoietic ontogeny. The first wave of hematopoiesis contains primitive erythroid, megakaryocyte and macrophage progenitors that arise in the yolk sac, and these macrophage progenitors are the source of early macrophages throughout the embryo, including the liver. A second wave of multipotential erythro-myeloid progenitors (EMPs) also arises in the yolk sac . EMPs colonize the fetal liver, initiating myelopoiesis and forming macrophages. Lineage tracing indicates that this second wave of macrophages are distributed in most fetal tissues, although not appreciably in the brain. Thus, fetal-derived adult tissue-resident macrophages, other than microglia, appear to predominately derive from EMPs. While HSCs emerge at midgestation and colonize the fetal liver, the relative contribution of fetal HSCs to tissue macrophages at later stages of development is unclear. The inclusion of macrophage potential in multiple waves of hematopoiesis is consistent with reports of their functional roles throughout development in innate immunity, phagocytosis, and tissue morphogenesis and remodeling. Understanding the influences of developmental origin, as well as local tissue-specific signals, will be necessary to fully decode the diverse functions and responses of tissue-resident macrophages.

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Temporal-Spatial Resolution Fate Mapping Reveals Distinct Origins for Embryonic and Adult Microglia in Zebrafish

Cited by 151 publications

References 65 publications

Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development

Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development

An updated assessment of microglia depletion: current concepts and future directions

Early hematopoiesis and macrophage development

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