Epigenetic and Epitranscriptomic Factors Make a Mark on Hematopoietic Stem Cell Development
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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.
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.
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.
KeywordsHemogenic endothelium HSC production Endothelial to hematopoietic transition Chromatin modification m6A methylation Transdifferentiation
We apologize to those whose original work could not be cited due to space limitations. D.M.K. is supported by NHLBI F32HL132475 and NIDDK U54DK106857.
Compliance with Ethical Standards
Conflict of Interest
Dionna M. Kasper and Stefania Nicoli declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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