Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 16:13:968228.
doi: 10.3389/fgene.2022.968228. eCollection 2022.

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

Mohammed Al-Obaide  1   2 , Albi Ishmakej  1   2 , Christina Brown  1   2 , Matteo Mazzella  1   2 , Patrina Agosta  3 , Mick Perez-Cruet  2   4 , G Rasul Chaudhry  1   2
Affiliations

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

Mohammed Al-Obaide et al. Front Genet. .

Abstract

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.

Keywords: integrin alpha 6; integrin alpha 6-antisense 1; lncRNA; mesenchymal stem cells; promoters; self-renewal.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Characteristics including cell size, doubling time, CFE, and differentiation potential of human MSCs from six sources, BM. PC, CH, CT, WJ, and CPJ. The ITGA6 is mapped at chr2:172,427,336–172,506,459 forward strand. (B) ITGA6 genomic DNA hosts three lncRNA loci and ten promoters (P1 to P10) and the lncRNA are coded by the reverse strand (Data from NCBI-Gene and Ensembl databases). (C) The ITGA6-AS1 partial complementarity with 3′UTR of ITGA6 mRNA type 1/variant 1 (v1). (D) ITGA6-AS1 showed 65.4% alignment to 26 bp of ITGA6 exon 2 (E2). (E) Predicted miR sequence hsa-miR-AS1.1, for details, see Supplementary Table S6.
FIGURE 2
FIGURE 2
The predicted features of P10, bidirectional promoter. (A) P10 sequence shows transcription factors binding sites. (B) Identification of CpG Island in the P10 sequence. The following options were searched: Window size, 100; minimum sequence length, 150; minimum Obs/Exp CpG, >0.6; %C + %G, >50.00%.
FIGURE 3
FIGURE 3
The expression of ITGA6 in the MSCs. (A1–A6) The t-test showed no statistically significant difference in expressions of ITGA6-E1 and ITGA6-E2 in the same MSC, p > 0.05. (B–C) A one-way ANOVA revealed a statistically significant difference in the expressions of ITGA6-E1 and ITGA6-E2, respectively in the six MSCs, p < 0.05.
FIGURE 4
FIGURE 4
The expression of ITGA6-E1 and ITGA6-AS1 in MSCs. (A1–A6) Expression of ITGA6-E1 and ITGA6-AS1 in the same CPJ, WJ, CT, BM, CH and PC, respectively. (B1–B6) Expressions of ITGA6-E2 and ITGA6-AS1 in the same CPJ, WJ, CT, BM, CH and PC, respectively. (C) A one-way ANOVA revealed a statistically significant difference in ITGA6-AS1 expressions in the tested MSCs, p < 0.05. (D) Sketch showing correlation of ITGA6-AS1 and ITGA6 expressions in MSCs.
See this image and copyright information in PMC

References

    1. Akiyama S. K. (1996). Integrins in cell adhesion and signaling. Hum. Cell. 9, 181–186. - PubMed
    1. Al-Obaide M. A. I., Al O., Vasylyeva T. L. (2021). Unexplored regulatory sequences of divergently paired GLA and HNRNPH2 loci pertinent to Fabry disease in human kidney and skin cells: Presence of an active bidirectional promoter. Exp. Ther. Med. 21, 154. 10.3892/etm.2020.9586 - DOI - PMC - PubMed
    1. Assis-Ribas T., Forni M. F., Winnischofer S. M. B., Sogayar M. C., Trombetta-Lima M. (2018). Extracellular matrix dynamics during mesenchymal stem cells differentiation. Dev. Biol. 437, 63–74. 10.1016/j.ydbio.2018.03.002 - DOI - PubMed
    1. Ballantyne M. D., McDonald R. A., Baker A. H. (2016). lncRNA/MicroRNA interactions in the vasculature. Clin. Pharmacol. Ther. 99, 494–501. 10.1002/cpt.355 - DOI - PMC - PubMed
    1. Becerra-Bayona S. M., Guiza-Arguello V. R., Russell B., Höök M., Hahn M. S. (2018). Influence of collagen-based integrin α(1) and α(2) mediated signaling on human mesenchymal stem cell osteogenesis in three dimensional contexts. J. Biomed. Mat. Res. A 106, 2594–2604. 10.1002/jbm.a.36451 - DOI - PMC - PubMed