ArticleThe Journal of clinical investigation2022
Hematopoietic stem cell regeneration through paracrine regulation of the Wnt5a/Prox1 signaling axis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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
9 citing papers in PubMed, 12 citations in OpenAlex.
- Single-Cell Profiling Reveals a Protective WNT5A-ATF3-FOSB Signaling Axis in Hair Follicle Stem Cells During Androgenetic Alopecia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- PROX1-associated lymphatic reprogramming signatures in pediatric adamantinomatous craniopharyngioma: a comparative study with adult cases.Frontiers in pediatrics · 2026Article
- M1-BMDMs with Wnt5a deletion attenuate liver fibrosis by suppression of Wnt5a/Frizzled 2 axis in hepatic progenitors.Cell & bioscience · 2025Article
- HES1 is required for mouse fetal hematopoiesis.Stem cell research & therapy · 2024Article
- Article
- PGE2 Produced by Exogenous MSCs Promotes Immunoregulation in ARDS Induced by Highly Pathogenic Influenza A through Activation of the Wnt-β-Catenin Signaling Pathway.International journal of molecular sciences · 2023Review
- Lymphatic vasculature in the central nervous system.Frontiers in cell and developmental biology · 2023Review
- The quest for the holy grail: overcoming challenges in expanding human hematopoietic stem cells for clinical use.Stem cell investigation · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The crosstalk between the BM microenvironment (niche) and hematopoietic stem cells (HSCs) is critical for HSC regeneration. Here, we show that in mice, deletion of the Fanconi anemia (FA) genes Fanca and Fancc dampened HSC regeneration through direct effects on HSCs and indirect effects on BM niche cells. FA HSCs showed persistent upregulation of the Wnt target Prox1 in response to total body irradiation (TBI). Accordingly, lineage-specific deletion of Prox1 improved long-term repopulation of the irradiated FA HSCs. Forced expression of Prox1 in WT HSCs mimicked the defective repopulation phenotype of FA HSCs. WT mice but not FA mice showed significant induction by TBI of BM stromal Wnt5a protein. Mechanistically, FA proteins regulated stromal Wnt5a expression, possibly through modulating the Wnt5a transcription activator Pax2. Wnt5a treatment of irradiated FA mice enhanced HSC regeneration. Conversely, Wnt5a neutralization inhibited HSC regeneration after TBI. Wnt5a secreted by LepR+CXCL12+ BM stromal cells inhibited β-catenin accumulation, thereby repressing Prox1 transcription in irradiated HSCs. The detrimental effect of deregulated Wnt5a/Prox1 signaling on HSC regeneration was also observed in patients with FA and aged mice. Irradiation induced upregulation of Prox1 in the HSCs of aged mice, and deletion of Prox1 in aged HSCs improved HSC regeneration. Treatment of aged mice with Wnt5a enhanced hematopoietic repopulation. Collectively, these findings identified the paracrine Wnt5a/Prox1 signaling axis as a regulator of HSC regeneration under conditions of injury and aging.
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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.