GSE195973
Intermediate GATA3 expression renders a noncanonical ILC population in skin essential for hair follicle recycling
We find that the expression of GATA3 in skin ILCs is significantly lower than in conventional ILC2s of other tissues, indicating that the regulatory role of GATA3 may be different. Indeed, skin ILCs are still maintained after inducing Gata3 depletion in Gata3fl/flCreERT2 mice, when all ILC2s were gone. In addition, about 70% skin ILCs are found to experience ROR?t expression as reflected by ROR?t fate-mapping. And, conditional Gata3 depletion in the ROR?t fate-mapped skin ILCs does not affect their number as well. Therefore, in contrast to conventional ILC2s, GATA3 is not required for skin ILCs for their maintenance. The ROR?t fate-mapped skin ILCs have exhibited ILC3-like features. Single-cell transcriptome analysis further reveals that skin ILCs converge on a Ccr6+ ILC3-like state and an Il1rl1+ ILC2-like state. The regulatory role of GATA3 is crucial in the ILC3-like skin ILCs. It promotes the expression of their featured genes, while suppresses the expression of ILC2-like skin ILC featured genes. These ILC3-like skin ILCs locate in close proximity to hair follicles. During hair follicle recycling they migrate from isthmus to suprabulbar to promote the hair follicle growth. Whereas in absence of Gata3, the ILC3-like skin ILCs exhibit defective migration to the suprabulbar and reduced expression of the featured genes in this process. Together, our study evidence that skin ILCs are alternative to conventional ILC2s. In particular, we shed light on the function of GATA3 in promoting the specific gene expression in ILC3-like skin ILCs and regulating their crucial roles in hair follicle recycling, which will improve our knowledge about the involvement of ILCs in maintaining homeostasis of skin. Overall design: We want to identify different gene expression in ROR?tfm+ and ROR?tfm- skin ILCs from ROR?t-fm and ROR?t-fm?Gata3 mice. We want to  identify different gene expression in skin ILCs between C57BL/6  (WT) and Gata3fl/flCreERT2 mice after tamoxifen treatment to knockout Gata3. We also use scRNA-seq of skin ILC from ear and dorsal skin(Day 0 and Day 10 after depilation) to identify subgroups.