Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and Stereo-seq

Yin Zhang; Juan Shen; Wei Cheng; Bhaskar Roy; Ruizhen Zhao; Tailiang Chai; Yifei Sheng; Zhao Zhang; Xueting Chen; Weiming Liang; Weining Hu; Qijun Liao; Shanshan Pan; Wen Zhuang; Yangrui Zhang; Rouxi Chen; Junpu Mei; Hong Wei; Xiaodong Fang

doi:10.1016/j.jgg.2023.04.012

Volume 50 Issue 9

Sep. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(9): 688-701

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Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and Stereo-seq

doi: 10.1016/j.jgg.2023.04.012

a. College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China;
b. BGI-Shenzhen, Shenzhen, Guangdong 518083, China;
c. College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China;
d. BGI-Qingdao, BGI-Shenzhen, Qingdao, Shandong 266555, China;
e. BGI-Sanya, BGI-Shenzhen, Sanya, Hainan 572025, China;
f. Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China

Funds:

This study was funded by the National Natural Science Foundation of China (81700436) and the Science Technology and Innovation Committee of Shenzhen Municipality, China (SGDX20190919142801722). We are grateful to the funding committee for supporting this project. We also thank all members of the project team for all their hard work. Thanks to the dissection staff for their assistance during the sampling process.

Received Date: 2023-01-12
Revised Date: 2023-04-23
Accepted Date: 2023-04-24
Publish Date: 2023-05-06

Abstract

Abstract

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.
- scRNA-seq,
- Spatial transcriptome,
- GF mouse,
- Spleen structure,
- Microbiota,
- Immune function

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References(86)

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