Vitamin C is used to treat anaemia; however, the mechanism through which vitamin C promotes erythroid differentiation is not comprehensively understood. The erythroid differentiation induction system can reveal the differentiation mechanism and provide erythrocytes for clinical transfusion and anaemia treatment. This process can be promoted by adding small-molecule compounds. In this study, we added l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AA2P), a derivative of vitamin C, to an erythroid differentiation system induced from umbilical cord blood haematopoietic stem and progenitor cells and detected its effect on erythroid differentiation using single-cell transcription sequencing technology combined with non-targeted metabolism detection. AA2P increased the proportion of late basophilic erythroblasts, upregulating the expression of erythroid-related regulatory molecules GATA1, KLF1, ALAS2, and the globins HBG and HBB. is a target gene of AA2P, and knockdown affected the expression of globin-related genes. AA2P also increased glycolysis and decreased oxidative phosphorylation to facilitate terminal erythroid differentiation and enhanced the proliferation of early erythroid progenitors by altering the cell cycle. These results provide a reliable basis for using vitamin C to improve the efficiency of erythropoiesis and for the clinical treatment of anaemia.
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http://dx.doi.org/10.1093/lifemedi/lnad043 | DOI Listing |
J Vis Exp
January 2025
Barts Cancer Institute, Queen Mary University of London;
Erythropoiesis, a remarkably dynamic and efficient process responsible for generating the daily quota of red blood cells (approximately 280 ± 20 billion cells per day), is crucial for maintaining individual health. Any disruption in this pathway can have significant consequences, leading to health issues. According to the World Health Organization, an estimated 25% of the global population presents symptoms of anemia.
View Article and Find Full Text PDFBlood Adv
January 2025
Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Interferon alpha (IFNa) is approved for the therapy of patients (pts) with polycythemia vera (PV), a subtype of myeloproliferative neoplasms (MPN). Some pts achieve molecular responses (MR), but clonal factors sensitizing for MR remain elusive. We integrated colony formation and differentiation assays with single-cell RNA seq and genotyping in PV-derived cells vs.
View Article and Find Full Text PDFLife Med
June 2024
Department of Orthopedic Surgery, Xijing Hospital, Airforce Medical University, Xi'an 710032, China.
Age-induced abnormalities in bone metabolism disrupt the equilibrium between bone resorption and formation. This largely stems from disturbances in bone homeostasis, in which signaling pathways exert a significant regulatory influence. Aging compromises the functionality of the bone marrow mesenchymal stem cells (BMSCs), ultimately resulting in tissue dysfunction and pathological aging.
View Article and Find Full Text PDFInt J Surg Pathol
January 2025
Department of Pathology, Stanford Medical Center, Stanford, CA, USA.
Insulinoma-associated protein 1 (INSM1) is a relatively new immunostain used in the diagnostic assessment of tumors with neuroendocrine differentiation. While INSM1 positivity has been described in some non-neuroendocrine neoplasms, reactivity in red blood cells (RBCs) has only been anecdotally noted in one prior study without description of the degree/extent of staining. INSM1 staining in nucleated erythroid precursors has not been previously reported.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Biochemistry and Molecular Biology, College of Medicine, Center for Epigenetics, Genetics Institute, UF Health Cancer Center, Powell-Gene Therapy Center, University of Florida, Gainesville, Florida 32610. Electronic address:
Transcription factor TFII-I/GTF2I is ubiquitously expressed and has been shown to play a role in the differentiation of hematopoietic cells and in the response to various cellular stressors. We previously demonstrated that TFII-I acts as a repressor of adult β-globin gene transcription and positively regulates expression of stress response proteins, including ATF3. Here we analyzed the function of TFII-I in TF-1 cells during erythroid differentiation and in response to cellular stress, including unfolded protein response, hypoxia, and oxidative stress.
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