Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar;4(1):22-32.
Epub 2018 Feb 3.

Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development

Dionna M Kasper  1 , Stefania Nicoli  1   2   3
Affiliations

Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development

Dionna M Kasper et al. Curr Stem Cell Rep. 2018 Mar.

Abstract

Purpose of the review: Blood specification is a highly dynamic process, whereby committed hemogenic endothelial cells (ECs) progressively transdifferentiate into multipotent, self-renewing hematopoietic stem cells (HSCs). Massive changes in gene expression must occur to switch cell identity, however the factors that mediate such an effect were a mystery until recently. This review summarizes the higher-order mechanisms involved in endothelial to hematopoietic reprogramming identified thus far.

Recent findings: Accumulating evidence from mouse and zebrafish studies reveal that numerous chromatin-modifying (epigenetic) and RNA-modifying (epitranscriptomic) factors are required for the formation of HSCs from hemogenic endothelium. These genes function throughout the endothelial-hematopoietic transition, suggesting a dynamic interplay between 'epi'-machineries.

Summary: Epigenetic and epitranscriptomic regulation are key mechanisms for reshaping global EC gene expression patterns to those that support HSC production. Future studies that capture modification dynamics should bring us closer to a complete understanding of how HSCs transition from hemogenic endothelium at the molecular level.

Keywords: HSC production; chromatin modification; endothelial to hematopoietic transition; hemogenic endothelium; m6A methylation; transdifferentiation.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Dionna M. Kasper and Stefania Nicoli declare that they have no conflict of interest.

Figures

Fig 1
Fig 1
During the formation of HSCs from hemogenic endothelium, EC genes are progressively silenced (red gradient) at the same time HSC genes are gradually activated (green gradient). Epigenetic and epitranscriptomic machinery facilitate the transition of these expression programs by modifying chromatin or mRNA, respectively. EC genes will become repressed within silenced chromatin in the nucleus or m6A-modified EC transcripts will be degraded in the cytoplasm (left). Conversely, open chromatin will promote Pol II-mediated transcription (brown) of HSC genes (right). Well-characterized EHT epigenetic and epitranscriptomic factors (ovals) are schematized here with their respective modifying-activity as described in the text and in Table 1. Modifications are defined in the key.
See this image and copyright information in PMC

References

    1. Medvinsky A, Dzierzak E. Definitive hematopoiesis is autonomously initiated by the AGM region. Cell. 1996;86(6):897–906. - PubMed
    1. Jaffredo T, Gautier R, Eichmann A, Dieterlen-Lievre F. Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny. Development. 1998;125(22):4575–83. - PubMed
    1. Zovein AC, Hofmann JJ, Lynch M, French WJ, Turlo KA, Yang Y, et al. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell. 2008;3(6):625–36. doi: 10.1016/j.stem.2008.09.018. - DOI - PMC - PubMed
    1. Bertrand JY, Chi NC, Santoso B, Teng S, Stainier DY, Traver D. Haematopoietic stem cells derive directly from aortic endothelium during development. Nature. 2010;464(7285):108–11. doi: 10.1038/nature08738. - DOI - PMC - PubMed
    1. Boisset JC, van Cappellen W, Andrieu-Soler C, Galjart N, Dzierzak E, Robin C. In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium. Nature. 2010;464(7285):116–20. doi: 10.1038/nature08764. - DOI - PubMed

LinkOut - more resources