Gut microbes exhibit complex interactions with their hosts and shape an organism's immune system throughout its lifespan.As the largest secondary lymphoid organ,the spleen has a wide range of immunological functio...Gut microbes exhibit complex interactions with their hosts and shape an organism's immune system throughout its lifespan.As the largest secondary lymphoid organ,the spleen has a wide range of immunological functions.To explore the role of microbiota in regulating and shaping the spleen,we employ scRNA-seq and Stereo-seq technologies based on germ-free(GF)mice to detect differences in tissue size,anatomical structure,cell types,functions,and spatial molecular characteristics.We identify 18 cell types,9 subtypes of T cells,and 7 subtypes of B cells.Gene differential expression analysis reveals that the absence of microorganisms results in alterations in erythropoiesis within the red pulp region and congenital immune deficiency in the white pulp region.Stereo-seq results demonstrate a clear hierarchy of immune cells in the spleen,including marginal zone(MZ)macrophages,MZ B cells,follicular B cells and T cells,distributed in a well-defined pattern from outside to inside.However,this hierarchical structure is disturbed in GF mice.Ccr7 and Cxcl13 chemokines are specifically expressed in the spatial locations of T cells and B cells,respectively.We speculate that the microbiota may mediate the structural composition or partitioning of spleen immune cells by modulating the expression levels of chemokines.展开更多
基金funded by the National Natural Science Foundation of China(81700436)the Science Technology and Innovation Committee of Shenzhen Municipality,China(SGDX20190919142801722)。
文摘Gut microbes exhibit complex interactions with their hosts and shape an organism's immune system throughout its lifespan.As the largest secondary lymphoid organ,the spleen has a wide range of immunological functions.To explore the role of microbiota in regulating and shaping the spleen,we employ scRNA-seq and Stereo-seq technologies based on germ-free(GF)mice to detect differences in tissue size,anatomical structure,cell types,functions,and spatial molecular characteristics.We identify 18 cell types,9 subtypes of T cells,and 7 subtypes of B cells.Gene differential expression analysis reveals that the absence of microorganisms results in alterations in erythropoiesis within the red pulp region and congenital immune deficiency in the white pulp region.Stereo-seq results demonstrate a clear hierarchy of immune cells in the spleen,including marginal zone(MZ)macrophages,MZ B cells,follicular B cells and T cells,distributed in a well-defined pattern from outside to inside.However,this hierarchical structure is disturbed in GF mice.Ccr7 and Cxcl13 chemokines are specifically expressed in the spatial locations of T cells and B cells,respectively.We speculate that the microbiota may mediate the structural composition or partitioning of spleen immune cells by modulating the expression levels of chemokines.
