TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate.

  title={TFEB-mediated endolysosomal activity controls human hematopoietic stem cell fate.},
  author={Laura Garcia-Prat and Kerstin B Kaufmann and Florin Schneiter and Veronique Voisin and Alex Murison and Jocelyn S. Chen and Michelle A. Chan-Seng-Yue and Olga I. Gan and Jessica Mcleod and Sabrina A. Smith and Michelle Shoong and Darrien Parris and Kristele Pan and Andy G. X. Zeng and Gabriela Krivdova and Kinam Gupta and Shin-ichiro Takayanagi and Elvin Wagenblast and Weijia Wang and M. Lupien and Timm Schroeder and Stephanie Z Xie and John E. Dick},
  journal={Cell stem cell},

The new metabolic needs of hematopoietic stem cells.

Korean stem cells are endowed with high regenerative potential to supply mature blood cells throughout life, under steady state or stress conditions, and understanding how HSCs use metabolism for their functions will offer new opportunity for HSC-based therapies.

Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness

The role of the lysosome as a signaling platform is focused on with an emphasis on its function in integrating nutrient sensing with proliferation and cell cycle progression, as well as in stemness-related features, such as self-renewal and quiescence.

Lysosomes in Stem Cell Quiescence: A Potential Therapeutic Target in Acute Myeloid Leukemia

Lysosome’s involvement in the critical biological processes has rekindled clinical interest towards this organelle for treating various diseases, including cancer, and the functions and importance of targeting lysosomes in AML are summarized.

INPP4B drives lysosome biogenesis to restrict leukemic stem cell differentiation and promote leukemogenesis

The discovery of a novel pathway linking INPP4B, lysosomal biogenesis and leukemic stemness, provides a mechanism to explain the association of high Inpp4b expression with poor AML prognosis, and highlights novel patient stratification strategies and LSC-specificLeukemic therapies.

Hematopoietic stem cells are a reservoir for trained immunity in autoimmune disease

HSC is identified as a functional unit ofTI in chronic AD, increased T-cell costimulatory activity is established as a potentially pathogenic feature of TI in this setting, and it is shown that macrophages inherit reduced metabolic activity from AD-exposed HSC, suggesting metabolic activation and TI can be decoupled.

The Role of Nutrients in Maintaining Hematopoietic Stem Cells and Healthy Hematopoiesis for Life

A deeper understanding of the molecular mechanisms involved in nutrient-driven metabolism and stem cell homeostasis will point to new avenues of medical research and may furnish new agents for improving human health care.

Lipids and the cancer stemness regulatory system in acute myeloid leukemia.

The latest findings from studies of lipid function in LSCs are discussed, with a focus on sphingolipids (SLs) as stemness/lineage fate mediators in AML, and the balance of fatty acid anabolism and catabolism fueling metabolic flexibility and drug resistance inAML.

Invading Bacterial Pathogens Activate Transcription Factor EB in Epithelial Cells through the Amino Acid Starvation Pathway of mTORC1 Inhibition

It is demonstrated that TFEB is activated in nonimmune cells upon infection with bacterial pathogens through a pathway dependent on mTORC1 inhibition and RAG-GTPase activity, reflecting the importance of membrane damage and amino acid starvation responses during infection.

Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging

Human hematopoiesis at each end of the age spectrum, during embryonic and fetal development and on aging is reviewed, providing exemplars of recent progress in deciphering the increasingly complex cellular and molecular hematoietic landscapes in health and disease.



Metabolism as master of hematopoietic stem cell fate

A deeper understanding of precisely how specific modes of metabolism control HSC fate is of great biological interest, and will be critical to the development of new therapeutic strategies that target HSC division balance for the treatment of hematological disease.

Self-renewal of a purified Tie2+ hematopoietic stem cell population relies on mitochondrial clearance

It is demonstrated, by characterizing at the single-cell level a purified and minimally heterogeneous murine Tie2+ HSC population, that these top hierarchical HSCs preferentially undergo symmetric divisions and suggest potential methods of cell-fate manipulation through metabolic pathways.

Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

It is shown that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal and suppression of iron regulatory protein 2 (IRP2) accumulation in FB XL5-deficient mouse HSCs restores stem cell function, implicating IRP2 as a potential therapeutic target for human hematopoietic diseases associated withFBXL5 downregulation.

Human haematopoietic stem cell lineage commitment is a continuous process

Flow cytometric, transcriptomic and functional data at single-cell resolution are integrated to quantitatively map early differentiation of human HSCs towards lineage commitment and provide a basis for the understanding of haematopoietic malignancies.

A comprehensive single cell transcriptional landscape of human hematopoietic progenitors

A broader transcriptional profiling of bone marrow lineage negative hematopoietic progenitors that recovers a key missing branchpoint into basophils and expands the understanding of the underlying structure of early adult human haematopoiesis is provided.