Hematopoietic stem cell function in β-thalassemia is impaired and is rescued by targeting the bone marrow niche

Claudio Tripodo, Alessandro Gulino, Ivan Merelli, Maria Rosa Lidonnici, Stefano Beretta, Annamaria Aprile, Maurilio Ponzoni, Giuliana Ferrari, Mariangela Storto, Alessandro Rubinacci, Sarah Marktel, Alessandro Rubinacci, Maurilio Ponzoni, Isabella Villa, Giuliana Ferrari, Mariangela Storto

Risultato della ricerca: Articlepeer review

15 Citazioni (Scopus)


Hematopoietic stem cells (HSCs) are regulated by signals from the bone marrow (BM) niche, which tune hematopoiesis at steady state and in hematologic disorders. To understand the HSC-niche interactions in altered non-malignant homeostasis, we elected as a paradigm β-thalassemia, a hemoglobin disorder. In this severe congenital anemia, secondary alterations to the primary hemoglobin defect have a potential impact on HSC-niche crosstalk. Here we report that HSCs in thalassemic mice (th3) have an impaired function, caused by the interaction with an altered BM niche. The HSC self-renewal defect is rescued upon transplantation into a normal microenvironment, thus proving the active role of BM stroma. Consistently with the common finding of osteoporosis in patients, we found reduced bone deposition with decreased levels of parathyroid hormone (PTH), which is a key regulator of bone metabolism but also of HSC activity. In vivo activation of PTH signaling through the reestablished Jagged1 and osteopontin levels correlates with the rescue of the functional pool of th3 HSCs by correcting HSC-niche crosstalk. Reduced HSC quiescence is confirmed in thalassemic patients, along with altered features of the BM stromal niche. Our findings uncover a defect of HSCs in β-thalassemia induced by an altered BM microenvironment and provide new relevant insight for improving transplantation and gene therapy approaches.
Lingua originaleEnglish
Numero di pagine0
Stato di pubblicazionePublished - 2020

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2400.2403???
  • ???subjectarea.asjc.2700.2720???
  • ???subjectarea.asjc.1300.1307???


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