Publications

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis  (2023)

Authors:
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
Title:
CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis
Year:
2023
Type of item:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Language:
Inglese
Referee:
No
Name of journal:
HEMASPHERE
ISSN of journal:
2572-9241
N° Volume:
7
Number or Folder:
12
Page numbers:
1-19
Keyword:
CK2β ,Hematopoietic Stem Cell ,Erythropoiesis
Short description of contents:
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.
Product ID:
138920
Handle IRIS:
11562/1124189
Last Modified:
May 8, 2024
Bibliographic citation:
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. 122023pp. 1-19

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