The Orphan Nuclear Receptor NR4A1 Specifies a Distinct Subpopulation of Quiescent Myeloid-Biased Long-Term HSCs. (18th December 2014)

• Record Type: Journal Article
• Authors: Land, Ruben H.; Rayne, Anna K.; Vanderbeck, Ashley N.; Barlowe, Trevor S.; Manjunath, Shwetha; Gross, Matthew; Eiger, Sophie; Klein, Peter S.; Cunningham, Nicole R.; Huang, Jian; Emerson, Stephen G.; Punt, Jennifer A.
• Is Part Of: Stem cells. Volume 33:Number 1(2015:Jan.)
• Page Start: 278
• Page End: 288
• Publication Date: 2014-12-18
• Subjects: Hematopoiesis -- Hematopoietic stem cell -- NR4A1 (Nur77) -- PGE2 -- Myeloid bias -- Quiescence; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1852
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1 GFP BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin − Sca-1 + c-Kit + CD48 − CD150 + long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1 GFP+ and NR4A1 GFP− HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1 GFP+ HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs. Stem Cells 2015;33:278–288