Research Areas

Hematopoiesis or blood cell formation is a sophisticated biological process which occurs in discrete anatomical locations during development and culminates in the adult with the replenishable production of dozens of functionally divergent blood cells. Our research interests mainly focus on the cellular and molecular basis of hematopoietic stem cell, macrophage and macrophage-like metaphocyte development; the roles of microglia and metaphocytes in neuronal network and mucosal immunity.

Highlights

The Main Scientific Research Achievements include：

1. By employing the high-resolution temporal-Spatial fate-mapping method (LEGO system), our group, for the first time, demonstrated the dual origins of microglia in vertebrates, which challenged the current view that microglia in mouse are solely derived from primitive Yolk-Sac macrophages.

2. Via time-lapse live imaging and multiple genetic methods, we proved the key signals in the developing brain for peripheral macrophage colonization in in-vivo animals for the first time.

3. We identified a novel cell type (metaphocytes) on the skin, which arises from ectoderm and participates in the presentation of soluble antigens.

4. For the first time, we demonstrated the non-HSC origin of T cells during early embryo development.

As the first or corresponding author, Prof. WEN has now published about 30 papers on well-recognized Journals, such as Science, Cell, Developmental Cell, Journal of Experimental Medicine, Blood et at., which have been cited for hundreds of times. Prof. WEN has presided nearly 20 research projects from Research Grants Council (RGC) in Hong Kong.

Figure 1 The IR-LEGO-CreER-loxP Cell Labeling System. A 1,345 nm laser is focused on the selected tissue of a desired developmental stage of a Tg(hsp70:mCherry-T2a-CreERT2;coro1a:loxP-DsRedx-loxPGFP) transgenic fish to generate spatial-restricted heat shock, which induces local expression of CreER. Upon 4-OHT treatment, the CreER-mediated recombination of loxP sites occurs, leading to the induction of GFP expression in the macrophages derived from the heat-shocked region.

Figure 2 Origins of microglia in zebrafish. Embryonic microglia in zebrafish initiate from the rostral blood island (RBI). Adult microglia in zebrafish arise from the ventral wall of dorsal aorta (VDA). The RBI- and VDA-derived microglia are differentially regulated by Pu.1 and Runx1.

Figure 3 The identification of metaphocytes. Ectoderm-derived metaphocytes in zebrafish epidermis are myeloid-like cells. Unlike Langerhans cells, highly mobile metaphocytes lack phagocytosis ability. Metaphocytes capture external soluble antigens through transepithelial protrusions and present antigen to Langerhans cells via apoptosis-phagocytosis.

Honors

• 2019   Croucher Senior Research Fellowships, Hong Kong

• 2011   School of Science Research Award, Hong Kong University of Science & Technology

Related News

1. https://www.scmp.com/news/hong-kong/health-environment/article/2177142/fish-kept-hong-kong-university-could-hold-key

2. https://zhuanlan.zhihu.com/p/65164781

Selected Publications

1. Wu ST^#, Nguyen TML^#, Pan HR, Hassan S, Dai YM, Xu J, Wen ZL (2020) Two phenotypically and functionally distinct microglial populations in adult zebrafish. Science Advances 6:eabd1160.

2. Lin X, Zhou QX, Zhao CL, Lin GZ, Xu J, Wen ZL (2019) An ectoderm-derived myeloid-like cell population functions as antigen transporters for Langerhans cells in zebrafish epidermis. Developmental Cell 49:605-617.  

3. Tian Y, Xu J, Feng SC, He SC, Zhao SZ, Zhu L, Jin W, Dai YM, Luo LF, Qu JY, Wen ZL (2017) The first wave of T lymphopoiesis in zebrafish arises from aorta endothelium independent of hematopoietic stem cells. Journal of Experimental Medicine 214:3347-3360.

4. Xu J^#, Zhu L^#, He SC, Wu Y, Jin W, Yu T, Qu JY*, Wen ZL* (2015) Temporal-spatial resolution fate mapping reveals distinct origins for embryonic and adult microglia in zebrafish. Developmental Cell 34:632-641.

5. Jin H^#, Xu J^#, Wen ZL (2007) Migratory path of definitive hematopoietic stem/progenitor cells during zebrafish development. Blood 109:5209-5214.