Nuclear CD44 Mediated by Importin β Participated in Naïve Genes Transcriptional Regulation in C3A-iCSCs

Su, Ming; Wang, Peipei; Wang, Xuan; Zhang, Mingzhi; Wei, Shiruo; Liu, Kaiyu; Han, Shuo; Han, Xu; Deng, Yue; Shen, Li

doi:10.7150/ijbs.28235

Cited by 11 publications

(8 citation statements)

References 33 publications

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“…Interestingly, IL-8 further increased the mRNA and protein expression of CD44 in CD44 hi IPF MPCs ( Figure 6A ), but exerted only a modest effect on CD44 expression in CD44 lo IPF MPCs. Prior studies indicate that full-length CD44 can transit to the nucleus where it plays a role in cancer stem cell colony formation ( 16 – 19 ). Therefore, we next examined the effect of IL-8 on CD44 levels in nuclear and cytoplasmic fractions of CD44 hi IPF MPCs.…”

Section: Resultsmentioning

confidence: 99%

“…Our data indicate that these cells have high levels of full-length CD44 within their nucleus. Prior studies have demonstrated that when the CD44 receptor is ligated, full-length CD44 is internalized and transported to the nucleus where it regulates cellular functions ( 16 – 19 ). We discovered that IL-8 promotes full-length CD44 nuclear accumulation, a process not previously described.…”

Section: Discussionmentioning

confidence: 99%

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A CD44/Brg1 nuclear complex confers mesenchymal progenitor cells with enhanced fibrogenicity in idiopathic pulmonary fibrosis

Yang¹,

Xia²,

Smith³

et al. 2021

JCI Insight

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Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease. We previously identified fibrogenic mesenchymal progenitor cells (MPCs) in the lungs of IPF patients that serve as drivers of progressive fibrosis. Recent single cell RNA sequencing work revealed that IPF MPCs with the highest transcriptomic network entropy differ the most from control MPCs; and that increased CD44 was a marker of these IPF MPCs. We hypothesize that IPF MPCs with high CD44 (CD44 hi ) expression will display enhanced fibrogenicity. We demonstrate that CD44 expressing MPCs are present at the periphery of the IPF fibroblastic focus, placing them in regions of active fibrogenesis. In a humanized mouse xenograft model, CD44 hi IPF MPCs are more fibrogenic than CD44 lo IPF MPCs and knock-down of CD44 diminishes their fibrogenicity. CD44 hi IPF MPCs display increased expression of pluripotency markers and enhanced self-renewal compared to CD44 lo IPF MPCs; properties potentiated by IL-8. The mechanism involves the accumulation of CD44 within the nucleus where it associates with the chromatin modulator protein BRG1 and the Zeb1 transcription factor. This CD44/BRG1/Zeb1 nuclear protein complex targets the Sox2 gene promoting its upregulation and self-renewal. Our data implicate CD44 interaction with the epigenetic modulator protein BRG1 in conveying IPF MPCs with cell-autonomous fibrogenicity.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A CD44/Brg1 nuclear complex confers mesenchymal progenitor cells with enhanced fibrogenicity in idiopathic pulmonary fibrosis

Yang¹,

Xia²,

Smith³

et al. 2021

JCI Insight

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“…In another study, CD44 depletion suppressed the proliferation of smooth muscle cells in mice as comparison to wild-type controls [14]. It has been evident that CD44 as a surface biomarker of cancer stem cells (CSCs) and a vital regulatory factor of epithelial-mesenchymal transition (EMT) program is involved in the regulation of tumor initiation and development [6,[15][16][17]. Aberrant expression of CD44 and dysregulation of CD44 contribute to tumor formation of multiple cancer entities, including lung cancer [18], hepatocellular carcinoma [19], ovarian cancer [20], glioma [21], papillary thyroid carcinoma [22], head and neck squamous cell carcinoma (HNSCC) [23], astrocytic gliomas [24] and oral squamous cell carcinoma (OSCC) [25].…”

Section: Open Accessmentioning

confidence: 99%

CD44 as a tumor biomarker and therapeutic target

et al. 2020

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CD44, a complex transmembrane glycoprotein, exists in multiple molecular forms, including the standard isoform CD44s and CD44 variant isoforms. CD44 participates in multiple physiological processes, and aberrant expression and dysregulation of CD44 contribute to tumor initiation and progression. CD44 represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is involved in the regulation of diverse vital signaling pathways that modulate cancer proliferation, invasion, metastasis and therapy-resistance, and it is also modulated by a variety of molecules in cancer cells. In addition, CD44 can serve as an adverse prognostic marker among cancer population. The pleiotropic roles of CD44 in carcinoma potentially offering new molecular target for therapeutic intervention. Preclinical and clinical trials for evaluating the pharmacokinetics, efficacy and drug-related toxicity of CD44 monoclonal antibody have been carried out among tumors with CD44 expression. In this review, we focus on current data relevant to CD44, and outline CD44 structure, the regulation of CD44, functional properties of CD44 in carcinogenesis and cancer progression as well as the potential CD44-targeting therapy for cancer management.

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“…It is highly possible that the scenario that takes place in mouse and rabbit ESCs will also occur in hESCs and hiPSCs. Additionally, GBX2 was reported as a naïve pluripotent marker along with KLF4, NANOG and MYC, which drive the transition of EpiSCs to ESCs [24][25][26] . Altogether, this suggests that Gbx2 is an essential pluripotent protein that promotes cell reprogramming and maintains self-renewal.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential transcription factors that enhance human iPSC generation

Swaidan

Salloum-Asfar

Palangi

et al. 2020

Sci Rep

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Although many factors have been identified and used to enhance the iPSC reprogramming process, its efficiency remains quite low. In addition, reprogramming efficacy has been evidenced to be affected by disease mutations that are present in patient samples. In this study, using RNA-seq platform we have identified and validated the differential gene expression of five transcription factors (TFs) (GBX2, NANOGP8, SP8, PEG3, and ZIC1) that were associated with a remarkable increase in the number of iPSC colonies generated from a patient with Parkinson's disease. We have applied different bioinformatics tools (Gene ontology, protein–protein interaction, and signaling pathways analyses) to investigate the possible roles of these TFs in pluripotency and developmental process. Interestingly, GBX2, NANOGP8, SP8, PEG3, and ZIC1 were found to play a role in maintaining pluripotency, regulating self-renewal stages, and interacting with other factors that are involved in pluripotency regulation including OCT4, SOX2, NANOG, and KLF4. Therefore, the TFs identified in this study could be used as additional transcription factors that enhance reprogramming efficiency to boost iPSC generation technology.

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Nuclear CD44 Mediated by Importin β Participated in Naïve Genes Transcriptional Regulation in C3A-iCSCs

Cited by 11 publications

References 33 publications

A CD44/Brg1 nuclear complex confers mesenchymal progenitor cells with enhanced fibrogenicity in idiopathic pulmonary fibrosis

A CD44/Brg1 nuclear complex confers mesenchymal progenitor cells with enhanced fibrogenicity in idiopathic pulmonary fibrosis

CD44 as a tumor biomarker and therapeutic target

Identification of potential transcription factors that enhance human iPSC generation

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