| First Author | Zhou J | Year | 2019 |
| Journal | Cell Stem Cell | Volume | 24 |
| Issue | 2 | Pages | 285-298.e5 |
| PubMed ID | 30639035 | Mgi Jnum | J:286017 |
| Mgi Id | MGI:6389913 | Doi | 10.1016/j.stem.2018.11.023 |
| Citation | Zhou J, et al. (2019) Combined Single-Cell Profiling of lncRNAs and Functional Screening Reveals that H19 Is Pivotal for Embryonic Hematopoietic Stem Cell Development. Cell Stem Cell 24(2):285-298.e5 |
| abstractText | The generation of hematopoietic stem cells (HSCs) from embryonic endothelial precursors and pre-HSCs is precisely regulated by signaling pathways and transcription factors. Nevertheless, regulatory roles of non-coding RNAs remain unknown. Taking advantage of our ability to capture rare pre-HSCs and HSCs in vivo, we generated a single-cell landscape of long non-coding RNAs (lncRNAs) during HSC development. Combining bioinformatics and functional screening, we identified 6 lncRNAs influencing hematopoiesis in vitro. We further revealed that H19 lncRNA is pivotal for in vivo HSC emergence in aorta-gonads-mesonephros region. Early H19 lncRNA deficiency blocked endothelial-to-hematopoietic transition, which was independent of the H19-derived miR, miR-675. Moreover, H19-deficient pre-HSCs displayed promoter hypermethylation and concomitant downregulation of several master hematopoietic transcription factors, including Runx1 and Spi1. H19 deficiency increased the activity of S-adenosylhomocysteine hydrolase, a regulator of DNA methylation, which partially contributed to the observed hematopoietic defect. Our findings provide a resource for further analysis of lncRNAs in embryonic HSC development. |
