Contributions
Abstract: S1590
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 08:00 - 08:15
Location: Room A10
Background
A tight control of hematopoietic stem cell (HSC) fate is crucial for lifelong blood production. Therefore, a fine balance of quiescence, self-renewal, and differentiation is key to maintain the HSC pool and blood homeostasis. In recent years cellular metabolism has emerged as a crucial regulator of HSC fate. HSCs differ from their committed progeny by relying primarily on anaerobic glycolysis rather than mitochondrial oxidative phosphorylation for energy production. However, whether this change in the metabolic program is the cause or a consequence of the unique function of HSCs remains unknown.
Aims
Here we asked if mitochondrial activity can be used as a reliable readout for functional HSCs and if modulation of mitochondrial activity results in enhancement of HSC function.
Methods
We used in vivo long term blood reconstitution assays as a readout of HSC functionality.
Results
We previously demonstrated that modulation of mitochondrial metabolism affects HSC fate, by chemically uncoupling the electron transport chain we were able to maintain HSC function in culture conditions that normally induce rapid differentiation (Vannini N, Girotra M. et al., Nat Comm 2016). Moreover, we demonstrated that modulation of mitochondrial activity in ex-vivo cultured human HSCs, via NAD+ boosting agent Nicotinamide Riboside (NR), results in better long-term blood production in serially transplanted humanized mice (Under Revision). Here we proceeded to carry out a mini screen, using mitochondrial activity as readout, to identify novel metabolic modulators that can be used to enhance HSC activity and function.
Conclusion
Our data thus reveal a causal relationship between mitochondrial metabolism and fate choice of HSCs, and also provide a valuable tool to identify optimal ex vivo conditions for HSC expansion and improve the outcome for patients suffering from bone marrow insufficiency.
Session topic: 24. Hematopoiesis, stem cells and microenvironment
Keyword(s): Hematopoietic Stem Cell, Human CD34+ cell, Mitochondria, Stem cell marker
Abstract: S1590
Type: Oral Presentation
Presentation during EHA23: On Sunday, June 17, 2018 from 08:00 - 08:15
Location: Room A10
Background
A tight control of hematopoietic stem cell (HSC) fate is crucial for lifelong blood production. Therefore, a fine balance of quiescence, self-renewal, and differentiation is key to maintain the HSC pool and blood homeostasis. In recent years cellular metabolism has emerged as a crucial regulator of HSC fate. HSCs differ from their committed progeny by relying primarily on anaerobic glycolysis rather than mitochondrial oxidative phosphorylation for energy production. However, whether this change in the metabolic program is the cause or a consequence of the unique function of HSCs remains unknown.
Aims
Here we asked if mitochondrial activity can be used as a reliable readout for functional HSCs and if modulation of mitochondrial activity results in enhancement of HSC function.
Methods
We used in vivo long term blood reconstitution assays as a readout of HSC functionality.
Results
We previously demonstrated that modulation of mitochondrial metabolism affects HSC fate, by chemically uncoupling the electron transport chain we were able to maintain HSC function in culture conditions that normally induce rapid differentiation (Vannini N, Girotra M. et al., Nat Comm 2016). Moreover, we demonstrated that modulation of mitochondrial activity in ex-vivo cultured human HSCs, via NAD+ boosting agent Nicotinamide Riboside (NR), results in better long-term blood production in serially transplanted humanized mice (Under Revision). Here we proceeded to carry out a mini screen, using mitochondrial activity as readout, to identify novel metabolic modulators that can be used to enhance HSC activity and function.
Conclusion
Our data thus reveal a causal relationship between mitochondrial metabolism and fate choice of HSCs, and also provide a valuable tool to identify optimal ex vivo conditions for HSC expansion and improve the outcome for patients suffering from bone marrow insufficiency.
Session topic: 24. Hematopoiesis, stem cells and microenvironment
Keyword(s): Hematopoietic Stem Cell, Human CD34+ cell, Mitochondria, Stem cell marker