CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis
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 regulator...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
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| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000978 |
| _version_ | 1827264907372920832 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Laura Quotti Tubi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T19:16:31Z |
| format | Article |
| id | doaj.art-6e1c71ae37604efe985cb3fd2c504dab |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2025-03-22T03:53:31Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-6e1c71ae37604efe985cb3fd2c504dab2024-04-28T11:12:10ZengWileyHemaSphere2572-92412023-12-01712e97810.1097/HS9.0000000000000978202312000-00006CK2β Regulates Hematopoietic Stem Cell Biology and ErythropoiesisLaura Quotti Tubi0Sara Canovas Nunes1Elisa Mandato2Marco Pizzi3Nicola Vitulo4Mirco D’Agnolo5Raffaella Colombatti6Maddalena Martella7Maria Paola Boaro8Elena Doriguzzi Breatta9Anna Fregnani10Zaira Spinello11Mitja Nabergoj12Odile Filhol13Brigitte Boldyreff14Mattia Albiero15Gian Paolo Fadini16Carmela Gurrieri17Fabrizio Vianello18Gianpietro Semenzato19Sabrina Manni20Livio Trentin21Francesco Piazza221 Department of Medicine, Division of Hematology, University of Padova, Italy2 Laboratory of Normal and Malignant Hematopoiesis and Pathobiology of Myeloma and Lymphoma. Veneto Institute of Molecular Medicine (VIMM), Padova, Italy2 Laboratory of Normal and Malignant Hematopoiesis and Pathobiology of Myeloma and Lymphoma. Veneto Institute of Molecular Medicine (VIMM), Padova, Italy5 Department of Medicine, Cytopathology and Surgical Pathology Unit, University of Padova, Italy6 Department of Biotechnology, University of Verona, Italy7 Department of Women’s and Child’s Health, University of Padova, Italy7 Department of Women’s and Child’s Health, University of Padova, Italy7 Department of Women’s and Child’s Health, University of Padova, Italy7 Department of Women’s and Child’s Health, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy8 Hematology Service, Institut Central des Hôpitaux (ICH), Hôpital du Valais, Sion, Switzerland9 Institut National de la Santé Et de la Recherche Médicale (INSERM) U1036, Institute de Reserches en Technologies et Sciences pour le Vivant/Biologie du Cancer et de l’Infection, Grenoble, France10 Kinase Detect, Krusaa, Denmark11 Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy12 Veneto Institute of Molecular Medicine, Experimental Diabetology Lab, Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, Italy1 Department of Medicine, Division of Hematology, University of Padova, ItalyThe 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.http://journals.lww.com/10.1097/HS9.0000000000000978 |
| spellingShingle | 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 CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis HemaSphere |
| title | CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis |
| title_full | CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis |
| title_fullStr | CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis |
| title_full_unstemmed | CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis |
| title_short | CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis |
| title_sort | ck2β regulates hematopoietic stem cell biology and erythropoiesis |
| url | http://journals.lww.com/10.1097/HS9.0000000000000978 |
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