Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis

Fan Liu, Guoyan Cheng, Pierre Jacques Hamard, Sarah Greenblatt, Lan Wang, Na Man, Fabiana Perna, Haiming Xu, Madhavi Tadi, Luisa Luciani, Stephen D Nimer

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Epigenetic regulators play critical roles in normal hematopoiesis, and the activity of these enzymes is frequently altered in hematopoietic cancers. The major type II protein arginine methyltransferase PRMT5 catalyzes the formation of symmetric dimethyl arginine and has been implicated in various cellular processes, including pluripotency and tumorigenesis. Here, we generated Prmt5 conditional KO mice to evaluate the contribution of PRMT5 to adult hematopoiesis. Loss of PRMT5 triggered an initial but transient expansion of hematopoietic stem cells (HSCs); however, Prmt5 deletion resulted in a concurrent loss of hematopoietic progenitor cells (HPCs), leading to fatal BM aplasia. PRMT5-specific effects on hematopoiesis were cell intrinsic and depended on PRMT5 methyltransferase activity. We found that PRMT5-deficient hematopoietic stem and progenitor cells exhibited severely impaired cytokine signaling as well as upregulation of p53 and expression of its downstream targets. Together, our results demonstrate that PRMT5 plays distinct roles in the behavior of HSCs compared with HPCs and is essential for the maintenance of adult hematopoietic cells.

Original languageEnglish (US)
Pages (from-to)3532-3544
Number of pages13
JournalJournal of Clinical Investigation
Volume125
Issue number9
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Medicine(all)

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    Liu, F., Cheng, G., Hamard, P. J., Greenblatt, S., Wang, L., Man, N., Perna, F., Xu, H., Tadi, M., Luciani, L., & Nimer, S. D. (2015). Arginine methyltransferase PRMT5 is essential for sustaining normal adult hematopoiesis. Journal of Clinical Investigation, 125(9), 3532-3544. https://doi.org/10.1172/JCI81749