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Given the incomplete understanding of \u03b2-thalassemia pathogenesis, there is an urgent need to identify effective biomarkers to advance research, diagnosis, and treatment. This study aims to identify potential biomarkers for two key purposes: (1) diagnosing transfusion-dependent \u03b2-thalassemia (TDT) and (2) detecting iron overload complications, with a focus on functional markers that reflect iron metabolism dysregulation in TDT. This study integrates transcriptomic data from the Genome Sequence Archive dataset (CRA003639) with bioinformatics analysis to identify potential biomarkers associated with \u03b2-thalassemia. Subsequently, Hbb-bs and Hbb-bt double knockout mice were used to establish a \u03b2-thalassemia model, while C57BL\/6JCya mice served as the control group, to validate the identified biomarkers through animal experiments. Seventeen reliable cell subsets were identified through rigorous annotation and screening. Quantitative analysis revealed a decreased proportion of immune cells (natural killer [NK] cells, T cells, macrophages, neutrophils, and monocytes) and an increased proportion of erythroid cells in the \u03b2-thalassemia group. Cell subset analysis focused on subsets that closely communicated with erythroid cells. Enrichment analysis of driver genes in these subsets revealed iron metabolism\u2013related pathways in\n                    <jats:italic>Erythroid_02<\/jats:italic>\n                    and\n                    <jats:italic>Erythroid_03<\/jats:italic>\n                    , and a ferroptosis-related pathway in\n                    <jats:italic>Erythroid_05.<\/jats:italic>\n                    Thalassemia model mice exhibited stronger iron ion fluorescence signals in primary hepatocytes, increased levels of total iron, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , and Fe\n                    <jats:sup>3+<\/jats:sup>\n                    in liver tissue, and decreased serum iron (SI) levels, indicating iron metabolism disorders. Reverse transcription polymerase chain reaction (RT-PCR) results showed differential gene expression, with\n                    <jats:italic>BCL2L1<\/jats:italic>\n                    ,\n                    <jats:italic>Hepb1<\/jats:italic>\n                    , and\n                    <jats:italic>Prdx6<\/jats:italic>\n                    downregulated and\n                    <jats:italic>Spta1<\/jats:italic>\n                    and\n                    <jats:italic>Snca<\/jats:italic>\n                    upregulated in the TDT model group. This study comprehensively characterizes TDT at the cellular and molecular levels, offering insights into its pathogenesis and identifying potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1007\/s00277-025-06605-6","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T03:12:29Z","timestamp":1757992349000},"page":"4369-4384","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic biomarkers and crucial cell subsets of iron metabolism in Beta-Thalassemia: insights from bioinformatics and experimental validation"],"prefix":"10.1007","volume":"104","author":[{"given":"Renrong","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangxing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"issue":"1","key":"6605_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00967-2","volume":"7","author":"K Lai","year":"2017","unstructured":"Lai K, Huang G, Su L, He Y (2017) The prevalence of thalassemia in Mainland China: evidence from epidemiological surveys. 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