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Publication . Other literature type . Article . 2016

Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells

Marie-Claude Gaudreau; Damien Grapton; Anne Helness; Charles Vadnais; Jennifer Fraszczak; Peiman Shooshtarizadeh; Brian T. Wilhelm; +3 Authors
Open Access
Published: 01 Jun 2016 Journal: Scientific Reports, volume 6 (eissn: 2045-2322, Copyright policy )
Publisher: Nature Publishing Group
Country: Germany

AbstractThe proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of γH2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin-c-Kit+ fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways.

Subjects by Vocabulary

Medical Subject Headings: environment and public health

Microsoft Academic Graph classification: Propidium iodide chemistry.chemical_compound chemistry Programmed cell death Fas receptor Immunology Apoptosis Haematopoiesis Biology RNA-binding protein Stem cell Cell biology Blood cell medicine.anatomical_structure medicine


Article, Animals, Apoptosis, Cell Survival, Hematopoietic Stem Cells, Heterogeneous-Nuclear Ribonucleoprotein L, Mice, Mice, Knockout, Real-Time Polymerase Chain Reaction, Receptors, TNF-Related Apoptosis-Inducing Ligand, Stress, Physiological, Tumor Suppressor Protein p53, Multidisciplinary, 570

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