ArticleThe Journal of clinical investigation2019
TGFβ signaling underlies hematopoietic dysfunction and bone marrow failure in Shwachman-Diamond Syndrome.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Beyond Hematologic Malignancies: Colorectal Cancer as a Solid Tumor Manifestation of Inherited Bone Marrow Failure Syndromes.International journal of molecular sciences · 2025Review
- TGF-β inhibition restores hematopoiesis and immune balance via bone marrow EPCs in aplastic anemia.Experimental & molecular medicine · 2025Article
- Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes.Stem cells (Dayton, Ohio) · 2025Review
- The Molecular and Genetic Mechanisms of Inherited Bone Marrow Failure Syndromes: The Role of Inflammatory Cytokines in Their Pathogenesis.Biomolecules · 2023Review
- TGF-beta signal transduction: biology, function and therapy for diseases.Molecular biomedicine · 2022Review
- Inflammation fuels bone marrow exhaustion caused by Samd9l mutation.The Journal of clinical investigation · 2022Article
- Transforming growth factor-β signaling modifies the hematopoietic acute inflammatory response to drive bone marrow failure.Haematologica · 2022Article
- Transforming growth factor-β1/Thrombospondin-1/CD47 axis mediates dysfunction in CD34European journal of pharmacology · 2022Article
- DNA damage and repair in the hematopoietic system.Acta biochimica et biophysica Sinica · 2022Review
- Acquired and hereditary bone marrow failure: A mitochondrial perspective.Frontiers in oncology · 2022Review
- Arhgef2 regulates mitotic spindle orientation in hematopoietic stem cells and is essential for productive hematopoiesis.Blood advances · 2021Article
- Review
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
- Inhibition of TGFβ improves hematopoietic stem cell niche and ameliorates cancer-related anemia.Stem cell research & therapy · 2021Article
- MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia.Cell stem cell · 2021Article
- Inhibition of TGFβ1 and TGFβ3 promotes hematopoiesis in Fanconi anemia.Experimental hematology · 2021Article
- Recent Advances in the Development of TGF-β Signaling Inhibitors for Anticancer Therapy.Journal of cancer prevention · 2020Review
- Ribosomopathies: New Therapeutic Perspectives.Cells · 2020Review
- Article
- Inflammatory manifestations in patients with Shwachman-Diamond syndrome: A novel phenotype.American journal of medical genetics. Part A · 2020Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Shwachman-Diamond Syndrome (SDS) is a rare and clinically-heterogeneous bone marrow (BM) failure syndrome caused by mutations in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Although SDS was described over 50 years ago, the molecular pathogenesis is poorly understood due, in part, to the rarity and heterogeneity of the affected hematopoietic progenitors. To address this, we used single cell RNA sequencing to profile scant hematopoietic stem and progenitor cells from SDS patients. We generated a single cell map of early lineage commitment and found that SDS hematopoiesis was left-shifted with selective loss of granulocyte-monocyte progenitors. Transcriptional targets of transforming growth factor-beta (TGFβ) were dysregulated in SDS hematopoietic stem cells and multipotent progenitors, but not in lineage-committed progenitors. TGFβ inhibitors (AVID200 and SD208) increased hematopoietic colony formation of SDS patient BM. Finally, TGFβ3 and other TGFβ pathway members were elevated in SDS patient blood plasma. These data establish the TGFβ pathway as a novel candidate biomarker and therapeutic target in SDS and translate insights from single cell biology into a potential therapy.
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Registered trials
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