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Downregulation of SATB1 by miRNAs reduces megakaryocyte/erythroid progenitor expansion in preclinical models of Diamond-Blackfan anemia. | LitMetric

AI Article Synopsis

  • * The condition disrupts early erythropoiesis by negatively impacting the development of megakaryocyte/erythroid progenitors (MEPs).
  • * Researchers identified that the downregulation of a chromatin regulator called SATB1, influenced by certain miRNAs, affects MEP expansion, highlighting the complex effects of ribosomal insufficiency on various stages of blood cell differentiation.

Article Abstract

Diamond-Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome that is associated with anemia, congenital anomalies, and cancer predisposition. It is categorized as a ribosomopathy, because more than 80% or patients have haploinsufficiency of either a small or large subunit-associated ribosomal protein (RP). The erythroid pathology is due predominantly to a block and delay in early committed erythropoiesis with reduced megakaryocyte/erythroid progenitors (MEPs). To understand the molecular pathways leading to pathogenesis of DBA, we performed RNA sequencing on mRNA and miRNA from RPS19-deficient human hematopoietic stem and progenitor cells (HSPCs) and compared existing database documenting transcript fluctuations across stages of early normal erythropoiesis. We determined the chromatin regulator, SATB1 was prematurely downregulated through the coordinated action of upregulated miR-34 and miR-30 during differentiation in ribosomal insufficiency. Restoration of SATB1 rescued MEP expansion, leading to a modest improvement in erythroid and megakaryocyte expansion in RPS19 insufficiency. However, SATB1 expression did not affect expansion of committed erythroid progenitors, indicating ribosomal insufficiency affects multiple stages during erythroid differentiation.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255422PMC
http://dx.doi.org/10.1016/j.exphem.2022.04.005DOI Listing

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