Sang Wan Sim, Yuyeon Jang, Tae Sub Park, Byung-Chul Park, Young Mok Lee, Hyun Sik Jun
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Molecular mechanisms of aberrant neutrophil differentiation in glycogen storage disease type Ib.
Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction, is caused by a deficiency in glucose-6-phosphate transporter (G6PT). Neutropenia in GSD-Ib has been known to result from enhanced apoptosis of neutrophils. However, it has also been raised that neutrophil maturation arrest in the bone marrow would contribute to neutropenia. We now show that G6pt-/- mice exhibit severe neutropenia and impaired neutrophil differentiation in the bone marrow. To investigate the role of G6PT in myeloid progenitor cells, the G6PT gene was mutated using CRISPR/Cas9 system, and single cell-derived G6PT-/- human promyelocyte HL-60 cell lines were established. The G6PT-/- HL-60s exhibited impaired neutrophil differentiation, which is associated with two mechanisms: (i) abnormal lipid metabolism causing a delayed metabolic reprogramming and (ii) reduced nuclear transcriptional activity of peroxisome proliferator-activated receptor-γ (PPARγ) in G6PT-/- HL-60s. In this study, we demonstrated that G6PT is essential for neutrophil differentiation of myeloid progenitor cells and regulates PPARγ activity.
期刊介绍：
Berliner Journal für Soziologie (“Berlin Journal of Sociology”), edited by the Institute of Sociology at the Friedrich Schiller University Jena and the Institute of Social Sciences at the Humboldt University Berlin, publishes double-blind peer-reviewed articles on classical and modern theoretical approaches, essays on current problem areas of sociological discourse, and research notes presenting new empirical findings. Focussed issues and review essays reflect innovative developments within the German and international social sciences and inform about the state of research in central areas of sociology.
The journal was founded in 1991 on the initiative of the East German Society of Sociology. It views itself as a general sociological journal that publishes contributions from all research and subject areas of sociology. From the very beginning, the programmatic aim has been to provide a forum for the discussion and further development of sociological problems in the light of contemporary theoretical and social developments.
Two major topics have been at the journal''s core and will continue to shape its contents in the future: Transformation and Culture. The journal deals with the socio-ecological upheaval that modern societies are undergoing. Globalisation, changes in working society and lifestyles, digitalisation, social conflicts up to new wars, new challenges for democracy, populism and nationalism as well as gender relations are important topics of a renewed Great Transformation. Cultural sociology and comparative cultural research deal with developments in these fields in a special way. The BJS therefore continues to devote its attention to such perspectives.
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