PUBLICATION
Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity
- Authors
- Xia, J., Liu, M., Zhu, C., Liu, S., Ai, L., Ma, D., Zhu, P., Wang, L., Liu, F.
- ID
- ZDB-PUB-230405-51
- Date
- 2023
- Source
- Cell Research 33(6): 448-463 (Journal)
- Registered Authors
- Liu, Feng, Ma, Dongyuan, Wang, Lu
- Keywords
- none
- Datasets
- GEO:GSE186424, GEO:GSE186425, GEO:GSE186423, GEO:GSE186427, GEO:GSE226750
- MeSH Terms
-
- Animals
- Cell Differentiation
- Cell Lineage
- Hemangioblasts*
- Hematopoiesis/physiology
- Hematopoietic Stem Cells
- Humans
- Induced Pluripotent Stem Cells*
- Mammals
- Zebrafish
- PubMed
- 37016019 Full text @ Cell Res.
Citation
Xia, J., Liu, M., Zhu, C., Liu, S., Ai, L., Ma, D., Zhu, P., Wang, L., Liu, F. (2023) Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity. Cell Research. 33(6):448-463.
Abstract
Hematopoietic stem and progenitor cells (HSPCs) are considered as a heterogeneous population, but precisely when, where and how HSPC heterogeneity arises remain largely unclear. Here, using a combination of single-cell multi-omics, lineage tracing and functional assays, we show that embryonic HSPCs originate from heterogeneous hemogenic endothelial cells (HECs) during zebrafish embryogenesis. Integrated single-cell transcriptome and chromatin accessibility analysis demonstrates transcriptional heterogeneity and regulatory programs that prime lymphoid/myeloid fates at the HEC level. Importantly, spi2+ HECs give rise to lymphoid/myeloid-primed HSPCs (L/M-HSPCs) and display a stress-responsive function under acute inflammation. Moreover, we uncover that Spi2 is required for the formation of L/M-HSPCs through tightly controlling the endothelial-to-hematopoietic transition program. Finally, single-cell transcriptional comparison of zebrafish and human HECs and human induced pluripotent stem cell-based hematopoietic differentiation results support the evolutionary conservation of L/M-HECs and a conserved role of SPI1 (spi2 homolog in mammals) in humans. These results unveil the lineage origin, biological function and molecular determinant of HSPC heterogeneity and lay the foundation for new strategies for induction of transplantable lineage-primed HSPCs in vitro.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping