ArticleBlood2017
TGF-β-induced intracellular PAI-1 is responsible for retaining hematopoietic stem cells in the niche.
Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
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- Inflammatory macrophage-derived plasminogen activator inhibitor-1 exacerbates inflammation through efferocytosis inhibition.Cell death discovery · 2026Article
- Reexamining Fat: Exploring Diversity, Plasticity, Development, Functional Implication, and Therapeutic Options.International journal of molecular sciences · 2026Review
- PAI-1 is a common driver of aging and diverse diseases.Biomedical journal · 2026Review
- Differential effects of fetal bovine serum and human platelet lysate on mesenchymal stromal cell-mediated support of hematopoietic stem/progenitor cells: a functional and transcriptomic analysis.Stem cell research & therapy · 2025Article
- Stem Cell Niche Concept: Search for Current Expert Consensus.International journal of molecular sciences · 2025Review
- Damage of the Bone Marrow Stromal Precursors in Patients with Acute Leukemia at the Onset of the Disease and During Treatment.International journal of molecular sciences · 2024Article
- Protective effect of Huashi Baidu formula against AKI and active ingredients that target SphK1 and PAI-1.Chinese medicine · 2024Article
- Function and Regulation of Bone Marrow Adipose Tissue in Health and Disease: State of the Field and Clinical Considerations.Comprehensive Physiology · 2024Review
- Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1.Frontiers in immunology · 2024Article
- Qigui-Yishen decoction delays renal fibrosis in mice with chronic kidney disease by regulating TM and PAI-1.American journal of translational research · 2024Article
- miR-181a plays the tumor-suppressor role in chronic myeloid leukemia CD34Cellular and molecular life sciences : CMLS · 2023Article
- Article
- SigPrimedNet: A Signaling-Informed Neural Network for scRNA-seq Annotation of Known and Unknown Cell Types.Biology · 2023Article
- Aging, Plasminogen Activator Inhibitor 1, Brain Cell Senescence, and Alzheimer's Disease.Aging and disease · 2023Article
- Blood protein profiles related to preterm birth and retinopathy of prematurity.Pediatric research · 2022Article
- The Molecular Mechanisms of Intestinal Inflammation and Fibrosis in Crohn's Disease.Frontiers in physiology · 2022Review
- Biomechanical cues as master regulators of hematopoietic stem cell fate.Cellular and molecular life sciences : CMLS · 2021Review
- Angiogenesis: A Cellular Response to Traumatic Injury.Shock (Augusta, Ga.) · 2021Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
Hematopoietic stem and progenitor cells (HSPCs) reside in the supportive stromal niche in bone marrow (BM); when needed, however, they are rapidly mobilized into the circulation, suggesting that HSPCs are intrinsically highly motile but usually stay in the niche. We questioned what determines the motility of HSPCs. Here, we show that transforming growth factor (TGF)-β-induced intracellular plasminogen activator inhibitor (PAI)-1 activation is responsible for keeping HSPCs in the BM niche. We found that the expression of PAI-1, a downstream target of TGF-β signaling, was selectively augmented in niche-residing HSPCs. Functional inhibition of the TGF-β-PAI-1 signal increased MT1-MMP-dependent cellular motility, causing a detachment of HSPCs from the TGF-β-expressing niche cells, such as megakaryocytes. Furthermore, consistently high motility in PAI-1-deficient HSPCs was demonstrated by both a transwell migration assay and reciprocal transplantation experiments, indicating that intracellular, not extracellular, PAI-1 suppresses the motility of HSPCs, thereby causing them to stay in the niche. Mechanistically, intracellular PAI-1 inhibited the proteolytic activity of proprotein convertase Furin, diminishing MT1-MMP activity. This reduced expression of MT1-MMP in turn affected the expression levels of several adhesion/deadhesion molecules for determination of HSPC localization, such as CD44, VLA-4, and CXCR4, which then promoted the retention of HSPCs in the niche. Our findings open up a new field for the study of intracellular proteolysis as a regulatory mechanism of stem cell fate, which has the potential to improve clinical HSPC mobilization and transplantation protocols.
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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.