ArticleBlood2023
Neutral sphingomyelinase blockade enhances hematopoietic stem cell fitness through an integrated stress response.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Extracellular vesicle cargo dynamics in the bone marrow microenvironment: from hematopoietic homeostasis to malignant transformation.Extracellular vesicle · 2026Article
- Metabolism and HSC fate: what NADPH is made for.Trends in cell biology · 2025Review
- SMPD2 affects the prognosis of cancer patients by mediating lipid metabolism and the immune microenvironment.Discover oncology · 2025Article
- Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.World journal of cardiology · 2025Review
- CCR2 cooperativity promotes hematopoietic stem cell homing to the bone marrow.Science advances · 2024Article
- A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate.Cell stem cell · 2024Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Hematopoietic stem and progenitor cell (HSPC) transplantation serves as a curative therapy for many benign and malignant hematopoietic disorders and as a platform for gene therapy. However, growing needs for ex vivo manipulation of HSPC-graft products are limited by barriers in maintaining critical self-renewal and quiescence properties. The role of sphingolipid metabolism in safeguarding these essential cellular properties has been recently recognized, but not yet widely explored. Here, we demonstrate that pharmacologic and genetic inhibition of neutral sphingomyelinase 2 (nSMase-2) leads to sustained improvements in long-term competitive transplantation efficiency after ex vivo culture. Mechanistically, nSMase-2 blockade activates a canonical integrated stress response (ISR) and promotes metabolic quiescence in human and murine HSPCs. These adaptations result in part from disruption in sphingolipid metabolism that impairs the release of nSMase-2-dependent extracellular vesicles (EVs). The aggregate findings link EV trafficking and the ISR as a regulatory dyad guarding HSPC homeostasis and long-term fitness. Translationally, transient nSMase-2 inhibition enables ex vivo graft manipulation with enhanced HSPC potency.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.