Stomatal pores on the leaf surface control both the uptake of CO2 for photosynthesis and the loss of water during transpiration. Since the industrial revolution, decreases in stomatal numbers in parallel with increases in atmospheric CO2 concentration have provided evidence of plant responses to changes in CO2 levels caused by human activity. This inverse correlation between stomatal density and CO2 concentration also holds for fossil material from the past 400 million years and has provided clues to the causes of global extinction events. Here we report the identification of the Arabidopsis gene HIC (for high carbon dioxide), which encodes a negative regulator of stomatal development that responds to CO2 concentration. This gene encodes a putative 3-keto acyl coenzyme A synthase--an enzyme involved in the synthesis of very-long-chain fatty acids. Mutant hic plants exhibit up to a 42% increase in stomatal density in response to a doubling of CO2. Our results identify a gene involved in the signal transduction pathway responsible for controlling stomatal numbers at elevated CO2.

Human embryonic stem (hES) [1] cells offer the opportunity for the in vitro production of multiple cell types for use in regenerative medicine. A key to unlocking this potential is development of methods for controlling gene expression and, consequently, cell differentiation. One tool that might be exploited is RNA interference (RNAi) [2] to manipulate specific signaling pathways in a transient manner and so influence the selection of specific pathways of differentiation by a pluripotent stem cell. To explore this possibility we have used RNAi to determine whether the transcription factor Oct4 is required to maintain the undifferentiated state of hES cells, as well as human embryonal carcinoma (hEC) cells, their malignant equivalent from teratocarcinomas, and whether forced knockdown of Oct4 expression results in differentiation toward trophectoderm. Murine ES cells have been shown to depend on the correct levels of Oct4 expression for their maintenance of an undifferentiated stem cell phenotype, and they

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

OCT‐4 (also known as POU5F1) is a key regulator of self‐renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Although OCT‐4 has been introduced as a molecular marker for germ cell tumors, little is known about its expression in somatic cancers. Here, we have investigated the potential expression of OCT‐4 in bladder cancer. We used semiquantitative RT‐PCR to examine the expression of OCT‐4 in 32 tumors, 13 apparently nontumor tissues taken from the margin of tumors and 9 normal urothelial tissues. The expression of OCT‐4 at protein level was further determined by Western blotting and immunohistochemical (IHC) analysis. OCT‐4 expression was detected in almost all examined tumors (31/32), but at much lower level (p < 0.001) in some nonneoplastic samples (6/22). A significantly strong correlation of 0.6 has been observed between OCT‐4 expression and the presence of tumors (p < 0.001). Western blot analysis further confirmed the expression of OCT‐4 in tumor biopsies. According to IHC results, OCT‐4 is primarily localized in the nuclei of tumor cells, with no or low immunoreactivity in nontumor cells. Our study demonstrated, for the first time, the expression of OCT‐4 in bladder cancer and a further clue to the involvement of embryonic genes in carcinogenesis. © 2007 Wiley‐Liss, Inc.

Embryonal carcinoma (EC) cells are the stem cells of teratocarcinomas, and the malignant counterparts of embryonic stem (ES) cells derived from the inner cell mass of blastocyst-stage embryos, whether human or mouse. On prolonged culture in vitro, human ES cells acquire karyotypic changes that are also seen in human EC cells. They also 'adapt', proliferating faster and becoming easier to maintain with time in culture. Furthermore, when cells from such an 'adapted' culture were inoculated into a SCID (severe combined immunodeficient) mouse, we obtained a teratocarcinoma containing histologically recognizable stem cells, which grew out when the tumour was explanted into culture and exhibited properties of the starting ES cells. In these features, the 'adapted' ES cells resembled malignant EC cells. The results suggest that ES cells may develop in culture in ways that mimic changes occurring in EC cells during tumour progression.

Cellular immortality happens upon impairment of cell-cycle checkpoint pathways (p53/p16/pRb), reactivation or up-regulation of telomerase enzyme, or upregulation of some oncogenes or oncoproteins leading to a higher rate of cell division.There are also some other factors and mechanisms involved in immortalisation, which need to be discovered. Immortalisation of cells derived from different sources and establishment of immortal cell lines has proven useful in understanding the molecular pathways governing cell developmental cascades in eukaryotic, especially human, cells. After the breakthrough of achieving the immortal cells and understanding their critical importance in the field of molecular biology, intense efforts have been dedicated to establish cell lines useful for elucidating the functions of telomerase, developmental lineage of progenitors, self-renewal potency, cellular transformation, differentiation patterns and some bioprocesses, like odontogenesis. Meanwhile, discovering the exact mechanisms of immortality, a major challenge for science yet, is believed to open new gateways toward understanding and treatment of cancer in the long term. This review summarises the methods involved in establishing immortality, its advantages and the challenges still being faced in this field.

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. Electronic supplementary material The online version of this article (10.1186/s13046-019-1169-0) contains supplementary material, which is available to authorized users.

Embryonal carcinoma (EC) cells are the stem cells of teratocarcinomas, and the malignant counterparts of embryonic stem (ES) cells derived from the inner cell mass of blastocyst-stage embryos, whether human or mouse. On prolonged culture in vitro, human ES cells acquire karyotypic changes that are also seen in human EC cells. They also 'adapt', proliferating faster and becoming easier to maintain with time in culture. Furthermore, when cells from such an 'adapted' culture were inoculated into a SCID (severe combined immunodeficient) mouse, we obtained a teratocarcinoma containing histologically recognizable stem cells, which grew out when the tumour was explanted into culture and exhibited properties of the starting ES cells. In these features, the 'adapted' ES cells resembled malignant EC cells. The results suggest that ES cells may develop in culture in ways that mimic changes occurring in EC cells during tumour progression.