HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2

Zhou, Xingyu; Li, Mingsen; Huang, Haoyue; Chen, Keren; Yuan, Zhuning; Zhang, Xumeng; Nie, Yaping; Hu, Chen; Chen, Luxi; Mo, Delin

doi:10.1242/jcs.189944

Cited by 24 publications

(26 citation statements)

References 50 publications

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“…The short isoform of IGF2BP2, p62, is overexpressed in HCC with stem-like features and hypervascularization, and the livers of p62 transgenic mice highly express the stem cell marker DLK1 and generate tumors with more aggressive and stem-like phenotype [ 27 ]. Consistent with these observations in CSCs are the determinant roles of IGF2BP2 in the differentiation of NPCs [ 16 ] and myoblasts [ 131 , 132 ].…”

Section: Igf2bp2 and Cancer Stem Cellssupporting

confidence: 54%

The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

Cao

Huang

2018

Stem Cells International

124

128

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RNA-binding proteins (RBPs) mediate the localization, stability, and translation of the target transcripts and fine-tune the physiological functions of the proteins encoded. The insulin-like growth factor (IGF) 2 mRNA-binding protein (IGF2BP, IMP) family comprises three RBPs, IGF2BP1, IGF2BP2, and IGF2BP3, capable of associating with IGF2 and other transcripts and mediating their processing. IGF2BP2 represents the least understood member of this family of RBPs; however, it has been reported to participate in a wide range of physiological processes, such as embryonic development, neuronal differentiation, and metabolism. Its dysregulation is associated with insulin resistance, diabetes, and carcinogenesis and may potentially be a powerful biomarker and candidate target for relevant diseases. This review summarizes the structural features, regulation, and functions of IGF2BP2 and their association with cancer and cancer stem cells.

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Section: Igf2bp2 and Cancer Stem Cellssupporting

confidence: 54%

The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

Cao

Huang

2018

Stem Cells International

124

128

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“…However, in articular cartilage, loss of HMGB2 reduces the regeneration capacity of mesenchymal stem cells by increasing apoptosis (42). Similarly, knockdown of HMGB2 decreased the number of muscle stem (satellite) cells by inhibiting proliferation and stimulating differentiation, thereby leading to the impaired muscle regeneration (43). Our study showed that the functional effects of HMGB2 on HSCs and blood system are similar to those in mesenchymal and muscle stem cells.…”

Section: Discussionsupporting

confidence: 56%

Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenance

et al. 2019

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regulation by HMGB2 is required for hematopoietic stem cell maintenance. ABSTRACTHematopoietic stem cells provide life-long production of blood cells and undergo selfrenewal division in order to sustain the stem cell pool. Homeostatic maintenance of hematopoietic stem cell pool and blood cell production is vital for organismal survival. We previously reported that latexin is a negative regulator of hematopoietic stem cells in mice, whose natural variation in the expression is inversely correlated with hematopoietic stem cell number. However, the molecular mechanisms regulating latexin transcription remain largely unknown, and the genetic factors contributing to its natural variation are not clearly defined.Here we discovered a chromatin protein, high-mobility group protein B2, as a novel transcriptional suppressor of latexin by using DNA pull-down and mass spectrometry. Highmobility group protein B2 knockdown increases latexin expression at transcript and protein levels, and decreases hematopoietic stem cell number and regeneration capacity in vivo. Concomitant blockage of latexin activation significantly reverses these phenotypic changes,suggesting that latexin is one of the downstream targets and functional mediators of highmobility group protein B2. We further identified a functional single nucleotide polymorphism, rs31528793, in the latexin promoter that binds to high-mobility group protein B2 and affects the promoter activity. G allelic variation in rs31528793 associates with the higher latexin expression and lower hematopoietic stem cell number, whereas C allele indicates the lower latexin expression and higher stem cell number. This study, for the first time, reveal that latexin transcription is regulated by both trans-acting (high-mobility group protein B2) and cis-acting (single nucleotide polymorphism rs31528793) factors. It uncovers the functional role of naturally occurring genetic variants, in combination with epigenetic regulator, in determining differential gene expression and phenotypic diversity in hematopoietic stem cell population.

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“…In support of this, HMGB2 was reported to promote the proliferation of satellite cells, which are quiescent stem cells in the muscle, orchestrating muscle regeneration (Zhou et al, ). In that report, Insulin‐like growth factor‐2 mRNA‐binding protein (IGF2BP2), a member of the family of IGF2 mRNA‐binding proteins known to bind to various RNAs such as IGF2 for enhancement of its translation, was shown to be a downstream target of HMGB2 and to increase the production of proteins encoded by cell cycle‐related genes to evoke the activation of quiescent satellite cells.…”

Section: Discussionmentioning

confidence: 91%

HMGB2 expression is associated with transition from a quiescent to an activated state of adult neural stem cells

Kimura

Matsuda

Sakai

et al. 2017

Developmental Dynamics

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Background: Although quiescent neural stem cells (NSCs) in the adult hippocampus proliferate in response to neurogenic stimuli and subsequently give rise to new neurons continuously throughout life, misregulation of NSCs in pathological conditions, including aging, leads to the impairment of learning and memory. High mobility group B family 1 (HMGB1) and HMGB2, HMG family proteins that function as transcriptional activators through the modulation of chromatin structure, have been assumed to play some role in the regulation of adult NSCs; however, their precise functions and even expression patterns in the adult hippocampus remain elusive. Results: Here we show that expression of HMGB2 but not HMGB1 is restricted to the subset of NSCs and their progenitors. Furthermore, running, a well-known positive neurogenic stimulus, increased the proliferation of HMGB2-expressing cells, whereas aging was accompanied by a marked decrease in these cells. Intriguingly, HMGB2-expressing quiescent NSCs, which were shifted toward the proliferative state, were decreased as aging progressed. Conclusions: HMGB2 expression is strongly associated with transition from the quiescent to the proliferative state of NSCs, supporting the possibility that HMGB2 is involved in the regulation of adult neurogenesis and can be used as a novel marker to identify NSCs primed for activation in the adult hippocampus. Developmental Dynamics 247:229-238, 2018. V C 2017 Wiley Periodicals, Inc.

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HMGB2 regulates satellite-cell-mediated skeletal muscle regeneration through IGF2BP2

Cited by 24 publications

References 50 publications

The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenance

HMGB2 expression is associated with transition from a quiescent to an activated state of adult neural stem cells

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