Extrinsic modulation of integrin α6 and progenitor cell behavior in mesenchymal stem cells

Nieto‐Nicolau, Núria; Torre, Raquel M. de la; Fariñas, Óscar; Savio, Andrés; Vilarrodona, Anna; Casaroli-Marano, Ricardo P.

doi:10.1016/j.scr.2020.101899

Cited by 18 publications

(26 citation statements)

References 39 publications

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“…We observed moderate to strong cytoplasmic and membranous positivity of ITGA6 in tumor cells. ITGA6 expression can indicate the progenitor potential of mesenchymal stem cells (MSC) [48]. Recent studies have reported that high ITGA6 expression enhances invasion and tumor-initiating cell activities in metastatic breast cancer (MBC) [49], providing evidence for the value of ITGA6 as cancer stem cell marker.…”

Section: Resultsmentioning

confidence: 99%

Single-cell Sequencing Highlights Heterogeneity and Malignant Progression in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma

Zou

Sun

et al. 2022

Preprint

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Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors (TFs) along AK to cSCC progression. Immunohistochemistry (IHC) / immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.

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Section: Resultsmentioning

confidence: 99%

Single-cell Sequencing Highlights Heterogeneity and Malignant Progression in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma

Zou

Sun

et al. 2022

Preprint

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“…Our study of the six human MSCs provided evidence of a potential correlation between the ITGA6 and its antisense RNA, ITGA6-AS1, and MSCs characteristics for the first time. Elevated expression of ITGA6 in BM MSCs from different donors was correlated with high clonogenicity, migration, differentiation, low doubling time, and proliferation ( Nieto-Nicolau et al, 2020 ; ( Lee et al, 2009 ; Yu et al, 2012 ; Nystedt et al, 2013 ). However, our studies showed low ITGA6 expression, poor clonogenicity, and higher doubling time in BM MSCs.…”

Section: Discussionmentioning

confidence: 99%

“…The culture conditions, intracellular matrix (ICM), and extracellular matrix (ECM) of MSCs can influence genetic-epigenetic inheritance ( Maurer, 2011 ; Sullivan et al, 2014 ; Assis-Ribas et al, 2018 ; Matta et al, 2019 ). Genetic-epigenetic can also influence the MSC’s fate; differentiation into progenitors and terminally differentiated cells ( Teven et al, 2011 ; Cakouros and Gronthos, 2020 ; Nieto-Nicolau et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Among the ITGAs, ITGA6 , also known as CD49f, is a transmembrane glycoprotein adhesion receptor protein which show higher expression in bone marrow (BM) MSCs ( Nieto-Nicolau et al, 2020 ). Downregulation of ITGA6 impaired the cell proliferation and migration of BM-MSCs via the protein kinase B (AKT) pathway and the cell cycle inhibitor proteins p53 and p21 ( Nieto-Nicolau et al, 2020 ). Additionally, overexpression of ITGA6 was found to be associated with an osteoporotic vertebral fracture in elderly women ( Jales Neto et al, 2020 ), bone metastasis and ductal carcinoma ( Martin and Jiang, 2014 ), colon cancer-initiating cells ( Haraguchi et al, 2013 ), cervical squamous cell carcinoma ( Hou et al, 2015 ), and in the invasion, metastasis and poor prognosis in human gallbladder carcinoma ( Zhang et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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The potential role of integrin alpha 6 in human mesenchymal stem cells

et al. 2022

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Human mesenchymal stem cells (MSCs) are isolated from various adult and perinatal tissues. Although mesenchymal stem cells from multiple sources exhibit similar morphology and cell surface markers, they differ in their properties. In this study, we determined that the expression of integrin alpha 6 (ITGA6) and ITGA6 antisense RNA (ITGA6-AS1) correlates with the proliferation, cell size, and differentiation potential. The expression of ITGA6 was inversely correlated with ITGA6-AS1 in MSCs. The expression of ITGA6 was higher, but ITGA6-AS1 was lower in MSCs from cord placenta junction, cord tissue, and Wharton’s jelly. In contrast, ITGA6 expression was lower, while ITGA6-AS1 was higher in MSCs from the placenta. The bioinformatic analysis showed that ITGA6 genomic DNA transcribes ITGA6-AS1 from the reverse strand, overlapping ITGA6 exon-2. Additionally, we identify several putative promoters (P1-P10) of ITGA6. ITGA6-P10 is CG rich and contains CGI. EMBOSS Cpgplot software revealed a CGI length of 180 bp that extends from nucleotide 125 to 304 of the P10 sequence. We suggest that the post-transcriptional regulation of the ITGA6 in mesenchymal stem cells is controlled by the ITGA6-AS1, which could be a critical factor responsible for the heterogeneity in function and cell fate of human MSCs. These results may provide further impetus for investigations to unravel the mechanisms of ITGA6 regulation that could help maintain or improve the properties of mesenchymal stem cells.

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Extracellular Vesicles Functional “Brick‐Cement” Bio‐Integrated System for Annulus Fibrosus Repair

Shen,

Pang,

Jiang

et al. 2024

Adv Funct Materials

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Due to the deficiency of mechanical supporting after discectomy and weak proliferative capacity of annulus fibrosus (AF) cells, the AF defect repair remains a clinical challenge. Herein, a myofibroblasts derived extracellular vesicles (M‐EVs) functional “brick‐cement” bio‐integrated system (M‐EVs@PGBgel) is developed to repair AF defect. The modified Poly(glycerol‐sebacate) (PGBS), “bio‐brick” layer, exhibited excellent support features on account of its elastomeric mechanical properties. The loaded M‐EVs in the “bio‐cement” layer activated ITGA6/PI3K/AKT pathway, regulated M2 macrophage polarization, thus synergistically promoting AF cell proliferation and migration. The “bio‐cement” layer integrated PGBS and remnant tissue at the defect through the Schiff base reaction and aided M‐EVs’ sustained release. This study demonstrated that M‐EVs@PGBgel significantly improved the disc's biological and mechanical properties in the AF defect microenvironments and promoted AF regeneration in vivo. The M‐EVs@PGBgel shows promise as an effective strategy to simultaneously address the mechanical imbalance and biological disruptions resulting from AF defect.

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Extrinsic modulation of integrin α6 and progenitor cell behavior in mesenchymal stem cells

Cited by 18 publications

References 39 publications

Single-cell Sequencing Highlights Heterogeneity and Malignant Progression in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma

Single-cell Sequencing Highlights Heterogeneity and Malignant Progression in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma

The potential role of integrin alpha 6 in human mesenchymal stem cells

Extracellular Vesicles Functional “Brick‐Cement” Bio‐Integrated System for Annulus Fibrosus Repair

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