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Background <p>Congenital dyserythropoietic anemia type I (CDA-I) is an autosomal recessive disorder marked by ineffective erythropoiesis, abnormal morphology of bone marrow erythroblasts, and iron overload. Most cases of CDA-I are caused by mutations in the CDAN1 gene, which encodes a ubiquitous protein of unknown function, Codanin-1.</p> Methods <p>To investigate the role of Codanin-1 in the molecular pathways involved in CDA-I, we developed erythroid models using human K562 cells and primary human CD34 + cells from mobilized peripheral blood.</p> Results <p>Here we show that Codanin-1 expression is required for erythroid progenitor development and normal erythroid cell differentiation. Erythroid cells lacking Codanin-1 demonstrated morphologic changes similar to those observed in CDA-I. Global gene expression changes after Codanin-1 knockdown revealed alterations in a set of key erythroid genes. In particular, the AHSP gene, which showed reduced mRNA and protein expression levels after Codanin-1 knockdown, also demonstrated increased Codanin-1 occupancy at its gene regulatory region by chromatin immunoprecipitation coupled to high-throughput sequencing.</p> Conclusion <p>In summary, using cell models recapitulating many features of CDA-I, we have studied and confirmed the importance of Codanin-1 during erythroid differentiation and provide mechanistic insight into how loss of Codanin-1 expression results in CDA-I.</p>

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Codanin-1, defective in congenital dyserythropoietic anemia I (CDA-I), regulates erythroid differentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Linette Bosques,
  • Susree Modepalli,
  • Arvindhan Nagarajan,
  • Caroline Tang,
  • Sandra Martínez-Morilla,
  • Nur-Taz Rahman,
  • Sameet S. Mehta,
  • Diane S. Krause,
  • Hannah Tamary,
  • Patrick G. Gallagher,
  • Shilpa M. Hattangadi,
  • Gary M. Kupfer

摘要

Background

Congenital dyserythropoietic anemia type I (CDA-I) is an autosomal recessive disorder marked by ineffective erythropoiesis, abnormal morphology of bone marrow erythroblasts, and iron overload. Most cases of CDA-I are caused by mutations in the CDAN1 gene, which encodes a ubiquitous protein of unknown function, Codanin-1.

Methods

To investigate the role of Codanin-1 in the molecular pathways involved in CDA-I, we developed erythroid models using human K562 cells and primary human CD34 + cells from mobilized peripheral blood.

Results

Here we show that Codanin-1 expression is required for erythroid progenitor development and normal erythroid cell differentiation. Erythroid cells lacking Codanin-1 demonstrated morphologic changes similar to those observed in CDA-I. Global gene expression changes after Codanin-1 knockdown revealed alterations in a set of key erythroid genes. In particular, the AHSP gene, which showed reduced mRNA and protein expression levels after Codanin-1 knockdown, also demonstrated increased Codanin-1 occupancy at its gene regulatory region by chromatin immunoprecipitation coupled to high-throughput sequencing.

Conclusion

In summary, using cell models recapitulating many features of CDA-I, we have studied and confirmed the importance of Codanin-1 during erythroid differentiation and provide mechanistic insight into how loss of Codanin-1 expression results in CDA-I.