Mechanistic roles of autophagy in hematopoietic differentiation

Riffelmacher, Thomas; Simon, Anna Katharina

doi:10.1111/febs.13962

Cited by 57 publications

(45 citation statements)

References 81 publications

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“…The metabolic features of the CD44 Low Kit Neg population were coupled with an increase in genes involved in autophagy. This is in line with the known role of autophagy in embryogenesis, haematopoiesis and stem cell maintenance [35][36][37]45,46 , such as protein and organelle turnover and protection from reactive oxygen species. Our data thus suggest that these cells mark the resetting of metabolic and regulatory states to initiate the EHT process.…”

Section: Discussionsupporting

confidence: 86%

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Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

et al. 2020

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The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening, we identify CD44 as a marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros (AGM) region. This allows us to provide a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which HSPCs emerge. They are characterized with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists, a downregulation of genes related to glycolysis and the TCA cycle, and a lower rate of cell cycle. Moreover, we demonstrate that by inhibiting the interaction between CD44 and its ligand hyaluronan, we can block EHT, identifying an additional regulator of HSPC development.

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Section: Discussionsupporting

confidence: 86%

“…Concordantly, two key processes accompanying autophagy, ubiquitylation and proteolysis, were also upregulated. As autophagy has been shown to play a key role in embryonic development and haematopoiesis [35][36][37] , this provides further support to the CD44 Low Kit Neg cells being in transit from endothelial to haematopoietic identity.…”

Section: Ssc-mentioning

confidence: 64%

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

et al. 2020

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“…The metabolic distinction of the CD44 Low Kit Neg population was coupled with an increase in genes involved in 14 autophagy. This is in line with the known role of autophagy in embryogenesis, haematopoiesis and stem cell maintenance [30][31][32]40,41 , such as protein and organelle turnover and protection from reactive oxygen species. Our data thus suggest that these cells mark the resetting of metabolic and regulatory states to initiate the EHT process.…”

Section: Discussionsupporting

confidence: 86%

Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development

Oatley

Öv

Svensson

et al. 2018

Preprint

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The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development.

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“…Autophagy-related (Atg) conjugation systems are a crucial element in this delivery process, along with the lysosomal degradation pathway, which contributes to cellular quality control through the elimination of functionally impaired organelles and proteins. When Atg7 has been conditionally depleted in hematopoietic systems, the resulting defects in autophagy have led to damaged mitochondria and lethal anemia [90, 91]. …”

Section: Metabolic Control In Hsc Homeostasis and Fate Decisionmentioning

confidence: 99%

Metabolism as master of hematopoietic stem cell fate

2018

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HSCs have a fate choice when they divide; they can self-renew, producing new HSCs, or produce daughter cells that will mature to become committed cells. Technical challenges, however, have long obscured the mechanics of these choices. Advances in flow-sorting have made possible the purification of HSC populations, but available HSC-enriched fractions still include substantial heterogeneity, and single HSCs have proven extremely difficult to track and observe. Advances in single-cell approaches, however, have led to the identification of a highly purified population of hematopoietic stem cells (HSCs) that make a critical contribution to hematopoietic homeostasis through a preference for self-renewing division. Metabolic cues are key regulators of this cell fate choice, and the importance of controlling the population and quality of mitochondria has recently been highlighted to maintain the equilibrium of HSC populations. Leukemic cells also demand tightly regulated metabolism, and shifting the division balance of leukemic cells toward commitment has been considered as a promising therapeutic strategy. A deeper understanding of precisely how specific modes of metabolism control HSC fate is, therefore, of great biological interest, and more importantly will be critical to the development of new therapeutic strategies that target HSC division balance for the treatment of hematological disease.

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Mechanistic roles of autophagy in hematopoietic differentiation

Cited by 57 publications

References 81 publications

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development

Metabolism as master of hematopoietic stem cell fate

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