Pubblicazioni

Autori:

Quotti Tubi, Laura; Canovas Nunes, Sara; Mandato, Elisa; Pizzi, Marco; Vitulo, Nicola; D’Agnolo, Mirco; Colombatti, Raffaella; Martella, Maddalena; Boaro, Maria Paola; Doriguzzi Breatta, Elena; Fregnani, Anna; Spinello, Zaira; Nabergoj, Mitja; Filhol, Odile; Boldyreff, Brigitte; Albiero, Mattia; Fadini, Gian Paolo; Gurrieri, Carmela; Vianello, Fabrizio; Semenzato, Gianpietro; Manni, Sabrina; Trentin, Livio; Piazza, Francesco

Titolo:

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis

Anno:

2023

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Referee:

No

Nome rivista:

HEMASPHERE

ISSN Rivista:

2572-9241

N° Volume:

7

Numero o Fascicolo:

12

Intervallo pagine:

1-19

Parole chiave:

CK2β ,Hematopoietic Stem Cell ,Erythropoiesis

Breve descrizione dei contenuti:

The Ser-Thr kinase CK2 plays important roles in sustaining cell survival and resistance to stress and these functions are exploited by different types of blood tumors. Yet, the physiological involvement of CK2 in normal blood cell development is poorly known. Here, we discovered that the beta regulatory subunit of CK2 is critical for normal hematopoiesis in the mouse. Fetal livers of conditional CK2 beta knockout embryos showed increased numbers of hematopoietic stem cells associated to a higher proliferation rate compared to control animals. Both hematopoietic stem and progenitor cells (HSPCs) displayed alterations in the expression of transcription factors involved in cell quiescence, self-renewal, and lineage commitment. HSPCs lacking CK2 beta were functionally impaired in supporting both in vitro and in vivo hematopoiesis as demonstrated by transplantation assays. Furthermore, KO mice developed anemia due to a reduced number of mature erythroid cells. This compartment was characterized by dysplasia, proliferative defects at early precursor stage, and apoptosis at late-stage erythroblasts. Erythroid cells exhibited a marked compromise of signaling cascades downstream of the cKit and erythropoietin receptor, with a defective activation of ERK/JNK, JAK/STAT5, and PI3K/AKT pathways and perturbations of several transcriptional programs as demonstrated by RNA-Seq analysis. Moreover, we unraveled an unforeseen molecular mechanism whereby CK2 sustains GATA1 stability and transcriptional proficiency. Thus, our work demonstrates new and crucial functions of CK2 in HSPC biology and in erythropoiesis.

Id prodotto:

138920

Handle IRIS:

11562/1124189

ultima modifica:

8 maggio 2024

Citazione bibliografica:

Quotti Tubi, Laura; Canovas Nunes, Sara; Mandato, Elisa; Pizzi, Marco; Vitulo, Nicola; D’Agnolo, Mirco; Colombatti, Raffaella; Martella, Maddalena; Boaro, Maria Paola; Doriguzzi Breatta, Elena; Fregnani, Anna; Spinello, Zaira; Nabergoj, Mitja; Filhol, Odile; Boldyreff, Brigitte; Albiero, Mattia; Fadini, Gian Paolo; Gurrieri, Carmela; Vianello, Fabrizio; Semenzato, Gianpietro; Manni, Sabrina; Trentin, Livio; Piazza, Francesco, CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis «HEMASPHERE» , vol. 7 , n. 12 , 2023 , pp. 1-19

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