HemaSphere (Dec 2023)

CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis

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

DOI
https://doi.org/10.1097/HS9.0000000000000978
Journal volume & issue
Vol. 7, no. 12
p. e978

Abstract

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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 β regulatory subunit of CK2 is critical for normal hematopoiesis in the mouse. Fetal livers of conditional CK2β 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 CK2β 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.