Format

Send to

Choose Destination
Cell Stem Cell. 2019 Mar 7;24(3):405-418.e7. doi: 10.1016/j.stem.2019.02.012.

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance.

Author information

1
Laboratory of Regenerative Hematopoiesis, Swiss Institute for Experimental Cancer Research (ISREC) & Institute of Bioengineering (IBI), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Epalinges 1066, Switzerland. Electronic address: nicola.vannini@unil.ch.
2
Laboratory of Regenerative Hematopoiesis, Swiss Institute for Experimental Cancer Research (ISREC) & Institute of Bioengineering (IBI), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
3
Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Epalinges 1066, Switzerland; Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
4
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
5
Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Epalinges 1066, Switzerland.
6
Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Epalinges 1066, Switzerland; Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
7
Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
8
Laboratory of System Biology and Genetics, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
9
Flow Cytometry Platform, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
10
Nestlé Research, EPFL Innovation Park, 1015 Lausanne, Switzerland.
11
Nestlé Research, EPFL Innovation Park, 1015 Lausanne, Switzerland; School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
12
Department of Obstetrics, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
13
Department of Oncology UNIL CHUV, Ludwig Institute for Cancer Research Lausanne, University of Lausanne, Epalinges 1066, Switzerland; Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences. Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
14
Service and Central Laboratory of Hematology, Departments of Oncology and of Laboratories, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
15
Service d'orthopédie et de traumatologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
16
Laboratory of Stem Cell Bioengineering, Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Institute of Chemical Sciences and Engineering, School of Basic Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
17
Laboratory of Regenerative Hematopoiesis, Swiss Institute for Experimental Cancer Research (ISREC) & Institute of Bioengineering (IBI), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Service and Central Laboratory of Hematology, Departments of Oncology and of Laboratories, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: olaia.naveiras@epfl.ch.

Abstract

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD+-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD+-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.

KEYWORDS:

HSC; UPRmt; aplastic anemia; asymmetric stem cell division; autophagy; bone marrow aplasia; bone marrow failure; bone marrow transplantation; chemotherapy; hematopoietic stem cell; hematopoietic stem cell transplantation; human CD34+ progenitors; immune thrombocytopenia; long-term hematopoietic stem cell; mitochondria; mitochondrial clearance; mitochondrial recycling; mitonuclear protein imbalance; mitophagy; myelodysplasia; myelodysplastic syndrome; radiotherapy; unfolded protein response mitochondria

PMID:
30849366
DOI:
10.1016/j.stem.2019.02.012

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center