Identification of in vitro HSC fate regulators by differential lipid raft clustering

Vannini, Nicola; Roch, Aline; Naveiras, Olaia; Griffa, Alessandra; Köbel, Stefan

doi:10.4161/cc.19900

Cited by 13 publications

(15 citation statements)

References 54 publications

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“…Using a previously established high-throughput clonal cell culture system, a microwell array 25, 26 , we analyzed by time-lapse microscopy approximately 50 single cells of each population over 5 days in culture in basal conditions 25 . The cell division patterns of single cells were observed to be strikingly different between the four populations (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells

et al. 2017

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The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell–cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.

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Section: Resultsmentioning

confidence: 99%

Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells

et al. 2017

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“…In support of this hypothesis, purified ST-HSCs from mice fed with a NR-supplemented diet showed no increase in cell-cycle entry ( Figure S6G). Single-cell tracking of NR-treated HSCs showed a significant increase in time-asynchronous divisions ( Figure 6A), which has been proposed as an epiphenomenon associated to increase asymmetric stem cell divisions (Vannini et al, 2012). We applied state-of-the-art single-cell analysis to evaluate NR-induced asymmetry of cell divisions in HSCs.…”

Section: Nr Promotes Asymmetric Mitochondrial Distribution In Lt-hscsmentioning

confidence: 97%

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

et al. 2019

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Graphical AbstractHighlights d Vitamin B3 analogs improve hematopoietic stem cell (HSC) and progenitor function d Nicotinamide riboside (NR) increases mitochondrial recycling in HSCs d In vitro NR exposure induces asymmetric mitochondrial distribution in dividing HSCs d NR dietary supplementation improves survival after HSC transplantation in mice SUMMARYIt 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.

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“…In neuroblastoma, the migration of vascular endothelial cells is associated with the induction of OPN, but not VEGF [51]. The two cytokines exert differential effects on lipid raft clustering (OPN suppresses, VEGF increases) and RAC (OPN inhibits, VEGF stimulates) [73].…”

Section: Discussionmentioning

confidence: 99%

“…Most hematopoietic stem cells in the bone marrow reside in a quiescent state and occasionally enter the cell cycle upon cytokine-induced activation. Lipid raft clustering is involved in hematopoietic stem cell activation, and OPN suppresses, whereas VEGF increases lipid raft clustering [73]. In contrast to the physiologic OPN-induced VEGF expression via PI3K/AKT/ERK [16], OPN secreted by glioma cells augments proliferation, migration and tube formation in endothelial progenitor cells via integrin α v β 3 /PI3K/AKT signaling, thus activating eNOS and increasing NO production, independently of changes in VEGF, VEGFR-1 and VEGFR-2 expression [37].…”

Section: Independent Actions Of Opn and Vegfmentioning

confidence: 99%

Interactions between osteopontin and vascular endothelial growth factor: Implications for cancer

Ramchandani

Weber

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Identification of in vitro HSC fate regulators by differential lipid raft clustering

Cited by 13 publications

References 54 publications

Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells

Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells

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

Interactions between osteopontin and vascular endothelial growth factor: Implications for cancer

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