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

First Author  Lu Y Year  2021
Journal  Cell Discov Volume  7
Issue  1 Pages  47
PubMed ID  34183665 Mgi Jnum  J:356124
Mgi Id  MGI:7762216 Doi  10.1038/s41421-021-00266-1
Citation  Lu Y, et al. (2021) Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture. Cell Discov 7(1):47
abstractText  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.
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