RNA Binding Protein Syncrip Is Required for the Low-Output HSC By Sustaining Proteome Quality

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.296-296
• Main Authors: Chavez, Florisela Herrejon, Cifani, Paolo, Pine, Alli, Chu, Karen L, Barin, Ersilia, Schurer, Alexandra, Luo, Hanzhi, Nguyen, Diu T.T., Kentsis, Alex, Leslie, Christina, Kharas, Michael G, Vu, Ly P
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-147575

RNA binding proteins (RBPs) have been increasingly recognized as an important class of regulators of normal and malignant hematopoiesis. However, the exact function and underpinning mechanisms of the RBPs that govern hematopoietic stem cells (HSCs) remains poorly characterized. We had previously identified SYNCRIP as a critical RBP that controls leukemia stem cell program in myeloid leukemia. Here, using the novel murine genetic conditional knockout (cKO) model, we delineated the role of SYNCRIP in regulating the low-output HSC. We developed a Syncrip cKO allele and crossed Syncripf/f mice to the interferon (IFN) -a-inducible Mx-1-Cre mice to create Syncripf/f Mx-1-Cre+. We consistently obtained near complete depletion of SYNCRIP 3 weeks after two consecutive Poly(I:C) injections. We observed that SYNCRIP is dispensable for static hematopoiesis and Syncrip KO animals showed equivalent number and frequencies of stem and progenitor cells (Lin-Sca+cKit+ (LSK)- LT-HSC (CD48-CD150+); MPP1 (CD48-CD150-); MPP2 (CD48+CD150+); MPP4 (CD48-CD150-)). However, KO SyncripD/D deficient cells were outcompeted by WT Syncripf/f cells in the transplantation setting (bone marrow (BM) chimerism WT (n=9) 38% ± 7.8% vs. KO (n=9) 2.7% ± 0.8%, p