Browsing by Author "Chumchuen S."

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    Author Correction: Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β0-thalassemia/HbE (Scientific Reports, (2022), 12, 1, (4952), 10.1038/s41598-022-08920-8)
    (2022-12-01) Wongborisuth C.; Chumchuen S.; Sripichai O.; Anurathaphan U.; Sathirapongsasuti N.; Songdej D.; Tangprasittipap A.; Hongeng S.; Mahidol University
    The original version of this Article contained an error in the spelling of the author Usanarat Anurathaphan which was incorrectly given as Anurathaphan Usanarat. The original Article has been corrected.
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    Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in β0-thalassemia/HbE
    (2022-12-01) Wongborisuth C.; Chumchuen S.; Sripichai O.; Anurathaphan U.; Sathirapongsasuti N.; Songdej D.; Tangprasittipap A.; Hongeng S.; Mahidol University
    Reactivating of fetal hemoglobin (HbF; α2γ2) can ameliorate the severity of β-thalassemia disease by compensating for adult hemoglobin deficiency in patients. Previously, microarray analysis revealed that zinc finger protein (ZNF)802 (also known as Juxta-posed with another zinc finger gene-1 (JAZF1)) was upregulated in human erythroblasts derived from adult peripheral blood compared with fetal liver-derived cells, implying a potential role as a HbF repressor. However, deficiency in ZNF802 induced by lentiviral shRNA in β0-thalassemia/hemoglobinE erythroblasts had no effect on erythroblast proliferation and differentiation. Remarkably, the induction of HBG expression was observed at the transcriptional and translational levels resulting in an increase of HbF to 35.0 ± 3.5%. Interestingly, the embryonic globin transcripts were also upregulated but the translation of embryonic globin was not detected. These results suggest ZNF802 might be a transcriptional repressor of the γ-globin gene in adult erythroid cells.
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    Downregulation of ZBTB7A/LRF increases fetal hemoglobin expression in β0-thalassemia/hemoglobin E erythroid cells
    (2025-12-01) Chumchuen S.; Pornsukjantra T.; Innachai P.; Khamphikham P.; Wongborisuth C.; Anurathapan U.; Songdej D.; Sripichai O.; Tangprasittipap A.; Hongeng S.; Chumchuen S.; Mahidol University
    Zinc finger and BTB domain-containing 7A (ZBTB7A) is a transcription factor repressor of fetal hemoglobin (HbF; α2γ2) in erythroid cells. Reactivating γ-globin expression represents a promising therapeutic strategy for β-hemoglobinopathies, including β-thalassemia. While ZBTB7A knockdown is known to elevate HbF levels in HUDEP-2 erythroid cell line and human hematopoietic stem/progenitor cell (HSPC)-derived erythroblasts, its effects in patient-derived cells remain less defined. This study investigates the effects of ZBTB7A downregulation in erythroid cells derived from both β0 thalassemia/hemoglobin E (β0-thal/HbE) patients and healthy donors. ZBTB7A knockdown upregulated embryonic and fetal globin genes (ε-, ζ-, γ-globin), and robust HbF induction while suppressing adult globin gene expression (α-, β-, δ-globin) in both groups. Notably, partial ZBTB7A inhibition was sufficient to achieve HbF reactivation. ZBTB7A depletion delayed erythroid maturation in healthy cells, but not in β⁰-thal/HbE cells, revealing a context-dependent effect on differentiation. These findings support ZBTB7A as a compelling target for β-thalassemia therapy, where partial inhibition could potentially offer therapeutic benefit while minimizing adverse effects on erythroid differentiation.
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    Effects of a short abstinence period on sperm quality in oligozoospermic men
    (2023-01-01) Poopaibool N.; Tangprasittipap A.; Chumchuen S.; Satirapod C.; Singwongsa A.; Mahidol University
    Objective: The aim of this study was to compare semen parameters and sperm DNA fragmentation (SDF) and explore the relationship between semen parameters and SDF between 2 and 7 days of abstinence and a short abstinence period (within 4 hours) in oligozoospermic infertile patients. Methods: Two semen samples were collected from infertile oligozoospermic men (n=34) after an abstinence period of 2 to 7 days and within 4 hours, respectively. Sperm parameters were compared between the two abstinence duration groups, including semen volume, sperm concentration, total sperm count, sperm motility, total motile sperm count (TMSC), morphology, and SDF. Results: The semen volume, concentration, and total sperm count were significantly decreased after 4 hours of abstinence than after 2 to 7 days of abstinence, with median differences of 1.2 mL (p<0.001), 2x106 /mL (p=0.011), and 9.6x106 /ejaculation (p<0.001), respectively. TMSC was significantly lower after a short abstinence, with a median difference of 4.24x106 /ejaculate (p<0.001). However, there were no significance differences in the percentage of motility, the SDF, and the percentage of sperm with normal morphology. Interestingly, volume, concentration, total sperm count, sperm motility, and SDF, but not TMSC, exhibited significant linear correlations between the two abstinence groups in univariate regression analysis, except for TMSC. Conclusion: In oligozoospermic men, the volume, concentration, and total sperm count were significantly lower after a short abstinence period, but without adverse effects on sperm motility and SDF.
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    Establishment of human induced pluripotent stem cell line MUi028-A from normal fetal skin fibroblasts
    (2022-04-01) Chumchuen S.; Satirapod C.; Tangprasittipap A.; Hongeng S.; Mahidol University
    MUi028-A human induced pluripotent stem cell (hiPSC) line was generated from normal fetal skin fibroblasts using a non-integrative reprogramming method. Reprogramming factors OCT4, SOX2, KLF4, L-MYC, and LIN28, and TP53 shRNA in three episomal vectors were delivered by electroporation. The MUi028-A cell line had embryonic stem cell characteristics with consistent expression of specific pluripotency markers and the capability of in vitro differentiation into the three germ layers. This iPSC line can be used as a control to study disease mechanisms.
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    Establishment of human induced pluripotent stem cell line MURAi001-A from skin fibroblasts of a patient carrying a c.4404A > G mutation in the TET1 gene
    (2024-09-01) Tangprasittipap A.; Innachai P.; Chumchuen S.; Chiangjong W.; Jinawath N.; Sirachainan N.; Hongeng S.; Tangprasittipap A.; Mahidol University
    Ten-Eleven Translocation methylcytosine dioxygenase 1 (TET1) is known to play a broad tumor suppressor role through demethylating and activating tumor suppressor genes. TET1 missense mutations are previously reported in many types of leukemia. Here, the human induced pluripotent stem cell line MURAi001-A was generated from skin fibroblasts derived from a 56-year-old female patient carrying the TET1 gene mutation c.4404A > G (p.I1468M), who had a history of ovarian germ cell tumor. The MURAi001-A cell line demonstrated embryonic-like characteristics as it expressed specific stemness markers, differentiated into the three germ layers, and retained normal karyotyping.
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    Generation of integration-free induced pluripotent stem cell (iPSC) line MURAi002-A from hemoglobin E/β-thalassemia disease patient harboring βE/β0 (CD41/42, –CTTT) compound heterozygous mutation
    (2025-08-01) Pornratananont G.; Tangprasittipap A.; Wongborisuth C.; Chumchuen S.; Bhukhai K.; Anurathapan U.; Hongeng S.; Songdej D.; Pornratananont G.; Mahidol University
    The HBB gene encodes the β-globin protein, a component of adult hemoglobin A (HbA) which is responsible for the transportation of oxygen. Mutations in the HBB gene can impair β-globin synthesis and disrupt hemoglobin production. Patients who possess both a protein-reducing β-thalassemia mutation and a βE mutation in their HBB gene are affected by hemoglobin E/β-thalassemia disease. This study demonstrates the successful generation and characterization of the human pluripotent stem cell (hiPSC) line MURAi002-A derived from a patient with hemoglobin E/β0-thalassemia disease harboring the specific codon 41/42 (−CTTT) β0-thalassemia mutation through the utilization of non-integrative reprogramming episomes.
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    In Vitro Study of Ineffective Erythropoiesis in Thalassemia: Diverse Intrinsic Pathophysiological Features of Erythroid Cells Derived from Various Thalassemia Syndromes
    (2022-09-01) Kaewsakulthong W.; Suriyun T.; Chumchuen S.; Anurathapan U.; Hongeng S.; Fucharoen S.; Sripichai O.; Mahidol University
    Defective hemoglobin production and ineffective erythropoiesis contribute to the pathophysiology of thalassemia syndromes. Previous studies in the field of erythropoiesis mainly focused on the severe forms of thalassemia, such as β-thalassemia major, while mechanisms underlying the pathogenesis of other thalassemia syndromes remain largely unexplored. The current study aimed to investigate the intrinsic pathophysiological properties of erythroid cells derived from the most common forms of thalassemia diseases, including α-thalassemia (hemoglobin H and hemoglobin H-Constant Spring diseases) and β-thalassemia (homozygous β0-thalassemia and β0-thalassemia/hemoglobin E diseases), under an identical in vitro erythroid culture system. Cell proliferation capacity, differentiation velocity, cell death, as well as globin synthesis and the expression levels of erythropoiesis modifying factors were determined. Accelerated expansion was found in erythroblast cells derived from all types of thalassemia, with the highest degree in β0-thalassemia/hemoglobin E. Likewise, all types of thalassemia showed limited erythroid cell differentiation, but each of them manifested varying degrees of erythroid maturation arrest corresponding with the clinical severity. Robust induction of HSP70 transcripts, an erythroid maturation-related factor, was found in both α- and β-thalassemia erythroid cells. Increased cell death was distinctly present only in homozygous β0-thalassemia erythroblasts and associated with the up-regulation of pro-apoptotic (Caspase 9, BAD, and MTCH1) genes and down-regulation of the anti-apoptotic BCL-XL gene.
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    Induction of fetal hemoglobin: Lentiviral shRNA knockdown of HBS1L in β0thalassemia/HbE erythroid cells
    (2023-03-01) Chumchuen S.; Sripichai O.; Jearawiriyapaisarn N.; Fucharoen S.; Peerapittayamongkol C.; Mahidol University
    Imbalanced globin chain output contributes to thalassemia pathophysiology. Hence, induction of fetal hemoglobin in β-thalassemia and other β-hemoglobinopathies are of continuing interest for therapeutic approaches. Genome-wide association studies have identified three common genetic loci: namely β-globin (HBB), an intergenic region between MYB and HBS1L, and BCL11A underlying quantitative fetal hemoglobin production. Here, we report that knockdown of HBS1L (all known variants) using shRNA in early erythroblast obtained from β0-thalassemia/HbE patients triggers an upregulation of γ-globin mRNA 1.69 folds. There is modest perturbation of red cell differentiation assessed by flow cytometry and morphology studies. The levels of α- and β-globin mRNAs are relatively unaltered. Knockdown of HBS1L also increases the percentage of fetal hemoglobin around 16.7 folds when compared to non-targeting shRNA. Targeting HBS1L is attractive because of the potent induction of fetal hemoglobin and the modest effect on cell differentiation.