Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture

被引：45

作者：

Lu, Yanfang ^{[1
,2
,3
]}

Liu, Miao ^{[1
]}

Yang, Jennifer ^{[1
]}

Weissman, Sherman M. ^{[1
]}

Pan, Xinghua ^{[2
,3
]}

Katz, Samuel G. ^{[4
]}

Wang, Siyuan ^{[1
,5
]}

机构：

[1] Yale Sch Med, Dept Genet, New Haven, CT 06510 USA

[2] Southern Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Guangzhou, Guangdong, Peoples R China

[3] Guangdong Prov Key Lab Single Cell Technol & Appl, Guangzhou, Guangdong, Peoples R China

[4] Yale Sch Med, Dept Pathol, New Haven, CT 06510 USA

[5] Yale Sch Med, Dept Cell Biol, New Haven, CT USA

来源：

CELL DISCOVERY | 2021年 / 7卷 / 01期

基金：

国家重点研发计划;

关键词：

SELF-RENEWAL; STROMAL CELLS; PROGENITOR CELLS; GROWTH-FACTOR; IN-VIVO; C-KIT; TET2; GENE; PROTEINS; MOUSE;

D O I：

10.1038/s41421-021-00266-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The hematopoietic stem cell (HSC) niche has been extensively studied in bone marrow, yet a more systematic investigation into the microenvironment regulation of hematopoiesis in fetal liver is necessary. Here we investigate the spatial organization and transcriptional profile of individual cells in both wild type (WT) and Tet2(-/-) fetal livers, by multiplexed error robust fluorescence in situ hybridization. We find that specific pairs of fetal liver cell types are preferentially positioned next to each other. Ligand-receptor signaling molecule pairs such as Kitl and Kit are enriched in neighboring cell types. The majority of HSCs are in direct contact with endothelial cells (ECs) in both WT and Tet2(-/-) fetal livers. Loss of Tet2 increases the number of HSCs, and upregulates Wnt and Notch signaling genes in the HSC niche. Two subtypes of ECs, arterial ECs and sinusoidal ECs, and other cell types contribute distinct signaling molecules to the HSC niche. Collectively, this study provides a comprehensive picture and bioinformatic foundation for HSC spatial regulation in fetal liver.

引用

页数：17

共 78 条

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