Spatial transcriptome profiling by MERFISH reveals fetal liver hematopoietic stem cell niche architecture
Open Access
- 29 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Discovery
- Vol. 7 (1), 1-17
- https://doi.org/10.1038/s41421-021-00266-1
Abstract
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.Keywords
This publication has 79 references indexed in Scilit:
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- Tet2 disruption leads to enhanced self-renewal and altered differentiation of fetal liver hematopoietic stem cellsScientific Reports, 2012
- Endothelial and perivascular cells maintain haematopoietic stem cellsNature, 2012
- Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in miceProceedings of the National Academy of Sciences of the United States of America, 2011
- Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid TransformationCancer Cell, 2011
- Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specificationNature, 2010
- Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cellsProceedings of the National Academy of Sciences of the United States of America, 2010
- Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRtNature Protocols, 2009
- Hematopoiesis: An Evolving Paradigm for Stem Cell BiologyCell, 2008
- Visualization of Single RNA Transcripts in SituScience, 1998