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Regulatory mechanisms in normal and malignant granulopoiesis
Kardošová, Miroslava ; Alberich Jorda, Meritxell (advisor) ; Stopka, Tomáš (referee) ; Balounová, Jana (referee)
Neutrophils, known primarily as key players in defense against invading pathogens, represent an essential component of both the innate and adaptive immunity. Continuous production of large quantities of neutrophils is ensured by a complex process termed granulopoiesis. In order to maintain a stable neutrophilic population, granulopoiesis requires to be tightly regulated. Moreover, impaired granulopoiesis may lead to aberrant bone marrow function and, ultimately, give rise to acute myeloid leukemia (AML). Despite decades of research, the mechanisms regulating granulopoiesis are still unclear. In particular, the CCAAT/enhancer binding protein (C/EBP) family of transcription factors plays a critical role in this process. C/EBPα acts as a master regulator of granulopoiesis mainly by orchestrating expression of its target genes, which will mediate granulocytic differentiation. Thus, characterization of novel C/EBPα target genes is critical for a better understanding of the molecular mechanisms that regulate granulopoiesis. Previously, we showed that another C/EBP member, CEBPG, is a direct target of C/EBPα. In the first part of the present work, we addressed the unknown role of C/EBPγ in granulopoiesis. We observed that Cebpg conditional knockout (KO) mice, which have the Cebpg gene ablated specifically...
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Regulatory mechanisms in normal and malignant granulopoiesis
Kardošová, Miroslava ; Alberich Jorda, Meritxell (advisor) ; Stopka, Tomáš (referee) ; Balounová, Jana (referee)
Neutrophils, known primarily as key players in defense against invading pathogens, represent an essential component of both the innate and adaptive immunity. Continuous production of large quantities of neutrophils is ensured by a complex process termed granulopoiesis. In order to maintain a stable neutrophilic population, granulopoiesis requires to be tightly regulated. Moreover, impaired granulopoiesis may lead to aberrant bone marrow function and, ultimately, give rise to acute myeloid leukemia (AML). Despite decades of research, the mechanisms regulating granulopoiesis are still unclear. In particular, the CCAAT/enhancer binding protein (C/EBP) family of transcription factors plays a critical role in this process. C/EBPα acts as a master regulator of granulopoiesis mainly by orchestrating expression of its target genes, which will mediate granulocytic differentiation. Thus, characterization of novel C/EBPα target genes is critical for a better understanding of the molecular mechanisms that regulate granulopoiesis. Previously, we showed that another C/EBP member, CEBPG, is a direct target of C/EBPα. In the first part of the present work, we addressed the unknown role of C/EBPγ in granulopoiesis. We observed that Cebpg conditional knockout (KO) mice, which have the Cebpg gene ablated specifically...
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