Scholarlink

<p>The hematopoietic stem cell and multipotent progenitor (HSC/MPP) pool dynamically responds to stress to adapt blood output to specific physiological demands. In β-thalassemia (Bthal), severe anemia and ineffective erythropoiesis generate expansion of erythroid precursors and a chronic stress status in the bone marrow (BM) microenvironment. However, the response to the BM altered status at the level of the HSC/MPP compartment in terms of lineage commitment has not been investigated. Bulk and single-cell RNA-sequencing reveal that Bthal HSCs/MPPs are expanded and activated with enhanced priming along the whole Ery differentiation trajectory. Consistently, HSC/MPP showed an altered TGFβ expression and autophagy transcriptional signatures along with a declined dormancy state. We discovered that the altered TGFβ signaling fosters the Ery potential of HSCs by reducing their autophagic levels, and in vivo stimulation of autophagy is sufficient to rescue the imbalance of the HSC compartment. Our findings identify the interplay between TGFβ and HSC autophagy as a key driver in the context of non-malignant hematopoiesis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Imbalanced TGFβ signalling and autophagy drive erythroid priming of hematopoietic stem cells in β-thalassemia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月1日

查看全文
  • Maria Rosa Lidonnici,
  • Giulia Chianella,
  • Nicole Mende,
  • Hugo P. Bastos,
  • Matteo Barcella,
  • Ivan Merelli,
  • Mariangela Storto,
  • Valentina Romeo,
  • Francesca Tiboni,
  • Samantha Scaramuzza,
  • Claudia Rossi,
  • Laura Raggi,
  • Annamaria Aprile,
  • Stefania Crippa,
  • Deena Iskander,
  • Irene Roberts,
  • Anastasios Karamiditris,
  • Julia Keith,
  • Christophe Lechauve,
  • Mitchell J. Weiss,
  • Nicola K. Wilson,
  • Berthold Göttgens,
  • Maria Ester Bernardo,
  • Fabio Ciceri,
  • Alessandro Aiuti,
  • Sarah Marktel,
  • Elisa Laurenti,
  • Giuliana Ferrari

摘要

The hematopoietic stem cell and multipotent progenitor (HSC/MPP) pool dynamically responds to stress to adapt blood output to specific physiological demands. In β-thalassemia (Bthal), severe anemia and ineffective erythropoiesis generate expansion of erythroid precursors and a chronic stress status in the bone marrow (BM) microenvironment. However, the response to the BM altered status at the level of the HSC/MPP compartment in terms of lineage commitment has not been investigated. Bulk and single-cell RNA-sequencing reveal that Bthal HSCs/MPPs are expanded and activated with enhanced priming along the whole Ery differentiation trajectory. Consistently, HSC/MPP showed an altered TGFβ expression and autophagy transcriptional signatures along with a declined dormancy state. We discovered that the altered TGFβ signaling fosters the Ery potential of HSCs by reducing their autophagic levels, and in vivo stimulation of autophagy is sufficient to rescue the imbalance of the HSC compartment. Our findings identify the interplay between TGFβ and HSC autophagy as a key driver in the context of non-malignant hematopoiesis.