Nuclear Tubulin Enhances CXCR4 Transcription and Promotes Chemotaxis Through TCF12 Transcription Factor in human Hematopoietic Stem Cells

Geng, Nanxi; Yu, Ziqin; Zeng, Xingchao; Xu, Dafeng; Gao, Huafang; Yang, Min; Huang, Xinxin

doi:10.1007/s12015-023-10543-z

Stem Cell Rev and Rep

2023

DOI: 10.1007/s12015-023-10543-z

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Nuclear Tubulin Enhances CXCR4 Transcription and Promotes Chemotaxis Through TCF12 Transcription Factor in human Hematopoietic Stem Cells

Nanxi Geng

Ziqin Yu

Xingchao Zeng

et al.

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2024

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Cited by 3 publications

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O‐GlcNAcylation regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum

Weng,

Wang,

Sitosari

et al. 2024

BioFactors

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To explore the potential mechanisms which O‐linked‐N‐acetylglucosaminylation (O‐GlcNAcylation) regulates osteogenesis, a publicly RNA‐seq dataset was re‐analyzed with literature‐mining and showed the primary targets of O‐GlcNAcylation in osteoblasts are mitochondria/cytoskeleton. Although the O‐GlcNAcylation‐regulated mitochondria/cytoskeleton has been extensively studied, its specific role during osteogenesis remains unclear. To address this, we knocked out Ogt (Ogt‐KO) in MC3T3‐E1 osteoblastic cells. Then, significantly reduced osteoblast differentiation, motility, proliferation, mitochondria–endoplasmic reticulum (Mito–ER) coupling, volume of ER, nuclear tubulins, and oxygen metabolism were observed in Ogt‐KO cells. Through artificial intelligence (AI)‐predicted cellular structures, the time‐lapse live cells imaging with reactive‐oxygen‐species/hypoxia staining showed that lower cell proliferation and altered oxygen metabolism in the Ogt‐KO cells were correlated with the Mito–ER coupling. Bioinformatics analysis, combined with correlated mRNA and protein expression, suggested that Ezh2 and its downstream targets (Opa1, Gsk3a, Wnt3a, Hif1a, and Hspa9) may be involved in O‐GlcNAcylation‐regulated Mito–ER coupling, ultimately impacting osteoblast differentiation. In conclusion, our findings indicate that O‐GlcNAcylation‐regulated osteoblast differentiation is linked to morphological changes in mitochondria, cytoskeleton, and ER, with Ezh2 potentially playing a crucial role.

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O‐GlcNAcylation regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum

Weng,

Wang,

Sitosari

et al. 2024

BioFactors

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Pulse Activation of Retinoic Acid Receptor Enhances Hematopoietic Stem Cell Homing by Controlling CXCR4 Membrane Presentation

Geng,

Yu,

Zeng

et al. 2024

Stem Cell Rev and Rep

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Molecular regulators of chemotaxis in human hematopoietic stem cells

Liu,

Geng,

Huang

2024

Biochemical Society Transactions

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Hematopoietic stem cells (HSCs), essential for lifelong blood cell regeneration, are clinically utilized to treat various hematological disorders. These cells originate in the aorta-gonad-mesonephros region, expand in the fetal liver, and mature in the bone marrow. Chemotaxis, involving gradient sensing, polarization, and migration, directs HSCs and is crucial for their homing and mobilization. The molecular regulation of HSC chemotaxis involves chemokines, chemokine receptors, signaling pathways, and cytoskeletal proteins. Recent advances in understanding these regulatory mechanisms have deepened insights into HSC development and hematopoiesis, offering new avenues for therapeutic innovations. Strategies including glucocorticoid receptor activation, modulation of histone acetylation, stimulation of nitric oxide signaling, and interference with m6A RNA modification have shown potential in enhancing CXCR4 expression, thereby improving the chemotactic response and homing capabilities of human HSCs. This review synthesizes current knowledge on the molecular regulation of human HSC chemotaxis and its implications for health and disease.

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Nuclear Tubulin Enhances CXCR4 Transcription and Promotes Chemotaxis Through TCF12 Transcription Factor in human Hematopoietic Stem Cells

Cited by 3 publications

References 46 publications

O‐GlcNAcylation regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum

O‐GlcNAcylation regulates osteoblast differentiation through the morphological changes in mitochondria, cytoskeleton, and endoplasmic reticulum

Pulse Activation of Retinoic Acid Receptor Enhances Hematopoietic Stem Cell Homing by Controlling CXCR4 Membrane Presentation

Molecular regulators of chemotaxis in human hematopoietic stem cells

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