ArticleStem cell research & therapy2021
EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC).
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.Nature medicine · 2023Trial
- Hematopoietic Aging and Leukemia: Mechanistic and Therapeutic Insights.International journal of molecular sciences · 2026Review
- Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia.Cancer discovery · 2026Article
- Identification and validation of a novel ferroptosis-related gene signature associated with inherited retinal degeneration in Rd10 mice.Scientific reports · 2026Article
- EGR1 Nuclear Condensates Promote Renal Cyst Development in Polycystic Kidney Disease.Exploration (Beijing, China) · 2026Article
- PURE-seq integrates FACS and PIP-seq for single-cell genomics of ultra-rare cells.Nature communications · 2026Article
- Targeting senescent EGR1Cell reports. Medicine · 2026Article
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- Hematopoietic Stem Cell Aging: Mechanisms, Microenvironment Influences, and Rejuvenation Strategies.Bioengineering (Basel, Switzerland) · 2025Review
- Targeting PURPL RNA enabled rejuvenation of senescence cells via epigenetic reprogramming.Journal of translational medicine · 2025Article
- AS04 drives superior cross-protective antibody response by increased NOTCH signaling of dendritic cells and proliferation of memory B cells.Frontiers in immunology · 2025Article
- Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PURE-seq identifiesbioRxiv : the preprint server for biology · 2024Article
- Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells.Nature genetics · 2024Article
- A germline point mutation in the MYC-FBW7 phosphodegron initiates hematopoietic malignancies.Genes & development · 2024Article
- Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
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- Article
- Male pattern hair loss: Can developmental origins explain the pattern?Experimental dermatology · 2023Article
- Unraveling Heterogeneity in the Aging Hematopoietic Stem Cell Compartment: An Insight From Single-cell Approaches.HemaSphere · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDuring aging, hematopoietic stem cells (HSC) lose progressively both their self-renewal and differentiation potential. The precise molecular mechanisms of this phenomenon are not well established. To uncover the molecular events underlying this event, we have performed a bioinformatics analysis of 650 single-cell transcriptomes.
methodsSingle-cell transcriptome analyses of expression heterogeneity, cell cycle, and cell trajectory in human cell compartment enriched in hematopoietic stem cell compartment were investigated in the bone marrow according to the age of the donors. Identification of aging-related nodules was identified by weighted correlation network analysis in this primitive compartment.
resultsThe analysis of single-cell transcriptomes allowed to uncover a major upregulation of EGR1 in human-aged lineage-CD34+CD38- cells which present cell cycle dysregulation with reduction of G2/M phase according to less expression of CCND2 during S phase. EGR1 upregulation in aging hematopoietic stem cells was found to be independent of cell cycle phases and gender. EGR1 expression trajectory in aged HSC highlighted a signature enriched in hematopoietic and immune disorders with the best induction of AP-1 complex and quiescence regulators such as EGR1, BTG2, JUNB, and NR41A. Sonic Hedgehog-related TMEM107 transmembrane molecule followed also EGR1 cell trajectory. EGR1-dependent gene weighted network analysis in human HSC-associated IER2 target protein-specific regulators of PP2A activity, IL1B, TNFSF10 ligands, and CD69, SELP membrane molecules in old HSC module with immune and leukemogenic signature. In contrast, for young HSC which were found with different cell cycle phase progression, its specific module highlighted upregulation of HIF1A hypoxic factor, PDE4B immune marker, DRAK2 (STK17B) T cell apoptosis regulator, and MYADM myeloid-associated marker.
conclusionEGR1 was found to be connected to the aging of human HSC and highlighted a specific cell trajectory contributing to the dysregulation of an inflammatory and leukemia-related transcriptional program in aged human HSCs. EGR1 and its program were found to be connected to the aging of human HSC with dissociation of quiescence property and cell cycle phase progression in this primitive hematopoietic compartment.
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