Stem Cell Niche Microenvironment: Review

yesThe cornea comprises a pool of self‐regenerating epithelial cells that are crucial to preserving clarity and visibility. Limbal epithelial stem cells (LESCs), which live in a specialized stem cell niche (SCN), are crucial for the survival of the human corneal epithelium. They live at the bottom of the limbal crypts, in a physically enclosed microenvironment with a number of neighboring niche cells. Scientists also simplified features of these diverse microenvironments for more analysis in situ by designing and recreating features of different SCNs. Recent methods for regenerating the corneal epithelium after serious trauma, including burns and allergic assaults, focus mainly on regenerating the LESCs. Mesenchymal stem cells, which can transform into self‐renewing and skeletal tissues, hold immense interest in tissue engineering and innovative medicinal exploration. This review summarizes all types of LESCs, identity and location of the human epithelial stem cells (HESCs), reconstruction of LSCN, and artificial stem cells for self‐renewal

Studying the expression patterns of OCT4 and SOX2 proteins in regenerating rabbit ear tissue

[EN] Epimorphic regeneration in New Zealand rabbit ear is an interesting example of mammalian wound healing in which blastema formation is involved in replacement of injured tissues. It has been suggested that isolated cells from regenerating rabbit ear possess stem-like properties. In this study, we aimed to determine the expression of stemness markers, OCT4 and SOX2 proteins, in regenerating rabbit tissues by immunohistochemistry. Results indicated that both proteins could be detected in epithelial cells, hair follicle cells and perichondrium cells. Expression pattern analysis of OCT4 and SOX2 proteins showed no clear differences between regenerative and non-regenerative control tissues. According to several reports of OCT4 and SOX2 proteins expression in adult stem cells, it could be proposed that OCT4 and SOX2 expressing cells in regenerating rabbit ear tissues are progenitor/adult stem cells which are resident in these tissues, and other markers should be used for detection of blastema cells.This work was supported by a grant (No. 6660) from Ferdowsi University of Mashhad, Iran. We appreciate Dr. Fatemeh B. Rassouli and Miss Malihe Akbarzadeh Niaki for their great technical support.Javanmard, AS.; Bahrami, AR.; Mahmoudi, Z.; Saeinasab, M.; Mahdavi-Shahri, N.; Matin, M. (2016). Studying the expression patterns of OCT4 and SOX2 proteins in regenerating rabbit ear tissue. World Rabbit Science. 24(2):155-164. doi:10.4995/wrs.2016.3965SWORD15516424

SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF

Background: Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types of cancers, however our understanding of their role in the disease is still very limited. Methods: We applied RNAseq analysis from patient-derived data with validation in independent cohort of patients. We followed these studies with gene regulation analysis as well as experimental dissection of the role of the identified lncRNA by multiple in vitro and in vivo methods. Results: We analyzed RNA-seq data from tumors of 456 CRC patients compared to normal samples, and identified SNHG15 as a potentially oncogenic lncRNA that encodes a snoRNA in one of its introns. The processed SNHG15 is overexpressed in CRC tumors and its expression is highly correlated with poor survival of patients. Interestingly, SNHG15 is more highly expressed in tumors with high levels of MYC expression, while MYC protein binds to two E-box motifs on SNHG15 sequence, indicating that SNHG15 transcription is directly regulated by the oncogene MYC. The depletion of SNHG15 by siRNA or CRISPR-Cas9 inhibits cell proliferation and invasion, decreases colony formation as well as the tumorigenic capacity of CRC cells, whereas its overexpression leads to opposite effects. Gene expression analysis performed upon SNHG15 inhibition showed changes in multiple relevant genes implicated in cancer progression, including MYC, NRAS, BAG3 or ERBB3. Several of these genes are functionally related to AIF, a protein that we found to specifically interact with SNHG15, suggesting that the SNHG15 acts, at least in part, by regulating the activity of AIF. Interestingly, ROS levels, which are directly regulated by AIF, show a significant reduction in SNHG15-depleted cells. Moreover, knockdown of SNHG15 increases the sensitiveness of the cells to 5-FU, while its overexpression renders them more resistant to the chemotherapeutic drug. Conclusion: Altogether, these results describe an important role of SNHG15 in promoting colon cancer and mediating drug resistance, suggesting its potential as prognostic marker and target for RNA-based therapies

Trial evaluation of bone marrow derived mesenchymal stem cells (MSCs) transplantation in revival of spermatogenesis in testicular torsion

Defective spermatogenesis due to the failure in germ cell proliferation and differentiation is the major sign of male infertility pathogenesis; and male factor is involved in up to half of all infertile couples. Testicular torsion is an acute vascular event causing the rotation of the vascular pedicle of the testis, thereby impeding the blood flow to the testis and the scrotal contents. Azoospermia caused by torsion in testis is a common source of impotency, which has not been touched by this approach, yet. Here, we use the capacity of mesenchymal stem cells (MSCs), as multipotent adult stem cells, to revive spermatogenesis in torsion-induced azoospermia. For this purpose, MSCs were extracted from rat bone marrow, cultured and transplanted into torsioned testis. Germ cell specific markers (Oct4, Vasa and c-Kit) were monitored for the differentiation of MSCs after transplantation into the torsion azoospermed testis. This study is a trial evaluation of mesenchymal stem cells in rat torsion testis to follow up the regenerative capacity of stem cells in spermatogenesis revival. These approaches can provide the powerful tools to investigate the basic biology of stem cells for reproductive engineering and infertility treatment

SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF

Abstract Background Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types of cancers, however our understanding of their role in the disease is still very limited. Methods We applied RNAseq analysis from patient-derived data with validation in independent cohort of patients. We followed these studies with gene regulation analysis as well as experimental dissection of the role of the identified lncRNA by multiple in vitro and in vivo methods. Results We analyzed RNA-seq data from tumors of 456 CRC patients compared to normal samples, and identified SNHG15 as a potentially oncogenic lncRNA that encodes a snoRNA in one of its introns. The processed SNHG15 is overexpressed in CRC tumors and its expression is highly correlated with poor survival of patients. Interestingly, SNHG15 is more highly expressed in tumors with high levels of MYC expression, while MYC protein binds to two E-box motifs on SNHG15 sequence, indicating that SNHG15 transcription is directly regulated by the oncogene MYC. The depletion of SNHG15 by siRNA or CRISPR-Cas9 inhibits cell proliferation and invasion, decreases colony formation as well as the tumorigenic capacity of CRC cells, whereas its overexpression leads to opposite effects. Gene expression analysis performed upon SNHG15 inhibition showed changes in multiple relevant genes implicated in cancer progression, including MYC, NRAS, BAG3 or ERBB3. Several of these genes are functionally related to AIF, a protein that we found to specifically interact with SNHG15, suggesting that the SNHG15 acts, at least in part, by regulating the activity of AIF. Interestingly, ROS levels, which are directly regulated by AIF, show a significant reduction in SNHG15-depleted cells. Moreover, knockdown of SNHG15 increases the sensitiveness of the cells to 5-FU, while its overexpression renders them more resistant to the chemotherapeutic drug. Conclusion Altogether, these results describe an important role of SNHG15 in promoting colon cancer and mediating drug resistance, suggesting its potential as prognostic marker and target for RNA-based therapies