ArticleCell stem cell2018
An ERK-Dependent Feedback Mechanism Prevents Hematopoietic Stem Cell Exhaustion.
Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
What it found
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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.
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Who cites it
71 citing papers in PubMed, 95 citations in OpenAlex.
- Hematopoietic Stem Cell Metabolism during Stress and Aging.Advances in geriatric medicine and research · 2026Article
- Article
- NCOA2 promotes the return of hematopoietic stem cells to quiescence after irradiation stress by regulating FOXO3a-dependent mitophagy.HemaSphere · 2026Article
- Critical role of niche S100A8 for acute myeloid leukemia progression and hematopoiesis regeneration.Blood advances · 2025Article
- RPL5 deficiency-induced ribosomal stress targets a select subset of proteins and inhibits the PI3K-Akt-mTOR signaling pathway to eradicate leukemia stem cells.Cell death & disease · 2025Article
- Mechanical cues orchestrate monocyte behavior in immune regulation and disease.APL bioengineering · 2025Review
- Maintenance of hematopoietic stem cells by tyrosine-unphosphorylated STAT5 and JAK inhibition.Blood advances · 2025Article
- Signaling proteins in HSC fate determination are unequally segregated during asymmetric cell division.The Journal of cell biology · 2024Article
- Bone Marrow Disseminated Tumor Cell Detection Is Beneficial for the Early Finding of Bone Metastasis and Prognosis.Diagnostics (Basel, Switzerland) · 2024Article
- tRNA mNature communications · 2024Article
- Label-free metabolic optical biomarkers track stem cell fate transition in real time.Science advances · 2024Article
- Chromatin accessibility and cell cycle progression are controlled by the HDAC-associated Sin3B protein in murine hematopoietic stem cells.Epigenetics & chromatin · 2024Article
- Article
- Article
- SPRY4-dependent ERK negative feedback demarcates functional adult stem cells in the male mouse germline†.Biology of reproduction · 2023Article
- The spatiotemporal heterogeneity of the biophysical microenvironment during hematopoietic stem cell development: from embryo to adult.Stem cell research & therapy · 2023Review
- Melanocortin/MC5R axis regulates the proliferation of hematopoietic stem cells in mice after ionizing radiation injury.Blood advances · 2023Article
- The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.The Journal of clinical investigation · 2023Article
- Article
- Cell-intrinsic factors governing quiescence vis-à-vis activation of adult hematopoietic stem cells.Molecular and cellular biochemistry · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Hematopoietic stem cells (HSCs) sustain hematopoiesis throughout life. HSCs exit dormancy to restore hemostasis in response to stressful events, such as acute blood loss, and must return to a quiescent state to prevent their exhaustion and resulting bone marrow failure. HSC activation is driven in part through the phosphatidylinositol 3-kinase (PI3K)/AKT/mTORC1 signaling pathway, but less is known about the cell-intrinsic pathways that control HSC dormancy. Here, we delineate an ERK-dependent, rate-limiting feedback mechanism that controls HSC fitness and their re-entry into quiescence. We show that the MEK/ERK and PI3K pathways are synchronously activated in HSCs during emergency hematopoiesis and that feedback phosphorylation of MEK1 by activated ERK counterbalances AKT/mTORC1 activation. Genetic or chemical ablation of this feedback loop tilts the balance between HSC dormancy and activation, increasing differentiated cell output and accelerating HSC exhaustion. These results suggest that MEK inhibitors developed for cancer therapy may find additional utility in controlling HSC activation.
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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.