Trichomes as models for studying plant cell differentiation

Trichomes, originating from epidermal cells, are present on nearly all terrestrial plants. They exist in diverse forms, are readily accessible, and serve as an excellent model system for analyzing the molecular mechanisms in plant cell differentiation, including cell fate choices, cell cycle control, and cell morphogenesis. In Arabidopsis, two regulatory models have been identified that function in parallel in trichome formation; the activator–inhibitor model and the activator–depletion model. Cotton fiber, a similar unicellular structure, is controlled by some functional homologues of Arabidopsis trichome-patterning genes. Multicellular trichomes, as in tobacco and tomato, may form through a distinct pathway from unicellular trichomes. Recent research has shown that cell cycle control participates in trichome formation. In this review, we summarize the molecular mechanisms involved in the formation of unicellular and multicellular trichomes, and discuss the integration of the cell cycle in its initiation and morphogenesis.     

Hsp90 regulation of mitochondrial protein folding: from organelle integrity to cellular homeostasis

Although essential for energy production and cell fate decisions, the mechanisms that govern protein homeostasis, or proteostasis, in mitochondria are only recently beginning to emerge. Fresh experimental evidence has uncovered a role of molecular chaperones of the heat shock protein 90 (Hsp90) family in overseeing the protein folding environment in mitochondria. Initially implicated in protection against cell death, there is now evidence that Hsp90-directed protein quality control in mitochondria connects to hosts of cellular homeostatic networks that become prominently exploited in human cancer.     

The common fragile site FRA16D gene product WWOX: roles in tumor suppression and genomic stability

The fragile WWOX gene, encompassing the chromosomal fragile site FRA16D, is frequently altered in human cancers. While vulnerable to DNA damage itself, recent evidence has shown that the WWOX protein is essential for proper DNA damage response (DDR). Furthermore, the gene product, WWOX, has been associated with multiple protein networks, highlighting its critical functions in normal cell homeostasis. Targeted deletion of Wwox in murine models suggests its in vivo requirement for proper growth, metabolism, and survival. Recent molecular and biochemical analyses of WWOX functions highlighted its role in modulating aerobic glycolysis and genomic stability. Cumulatively, we propose that the gene product of FRA16D, WWOX, is a functionally essential protein that is required for cell homeostasis and that its deletion has important consequences that contribute to the neoplastic process. This review discusses the essential role of WWOX in tumor suppression and genomic stability and how its alteration contributes to cancer transformation.     

Genetic studies of diseases

Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratory.     

A close look at the mammalian blastocyst: epiblast and primitive endoderm formation

During early development, the mammalian embryo undergoes a series of profound changes that lead to the formation of two extraembryonic tissues—the trophectoderm and the primitive endoderm. These tissues encapsulate the pluripotent epiblast at the time of implantation. The current model proposes that the formation of these lineages results from two consecutive binary cell fate decisions. The first controls the formation of the trophectoderm and the inner cell mass, and the second controls the formation of the primitive endoderm and the epiblast within the inner cell mass. While early mammalian embryos develop with extensive plasticity, the embryonic pattern prior to implantation is remarkably reproducible. Here, we review the molecular mechanisms driving the cell fate decision between primitive endoderm and epiblast in the mouse embryo and integrate data from recent studies into the current model of the molecular network regulating the segregation between these lineages and their subsequent differentiation.     

Molecular pathways driving disease-specific alterations of intestinal epithelial cells

Due to the fact that chronic inflammation as well as tumorigenesis in the gut is crucially impacted by the fate of intestinal epithelial cells, our article provides a comprehensive overview of the composition, function, regulation and homeostasis of the gut epithelium. In particular, we focus on those aspects which were found to be altered in the context of inflammatory bowel diseases or colorectal cancer and also discuss potential molecular targets for a disease-specific therapeutic intervention.     

The intestinal epithelium tuft cells: specification and function

The intestinal epithelium, composed of at least seven differentiated cell types, represents an extraordinary model to understand the details of multi-lineage differentiation, a question that is highly relevant in developmental biology as well as for clinical applications. This review focuses on intestinal epithelial tuft cells that have been acknowledged as a separate entity for more than 60?years but whose function remains a mystery. We discuss what is currently known about the molecular basis of tuft cell fate and differentiation and why elucidating tuft cell function has been so difficult. Finally, we summarize the current hypotheses on their potential involvement in diseases of the gastro-intestinal tract.     

The mammary cellular hierarchy and breast cancer

Advances in the study of hematopoietic cell maturation have paved the way to a deeper understanding the stem and progenitor cellular hierarchy in the mammary gland. The mammary epithelium, unlike the hematopoietic cellular hierarchy, sits in a complex niche where communication between epithelial cells and signals from the systemic hormonal milieu, as well as from extra-cellular matrix, influence cell fate decisions and contribute to tissue homeostasis. We review the discovery, definition and regulation of the mammary cellular hierarchy and we describe the development of the concepts that have guided our investigations. We outline recent advances in in vivo lineage tracing that is now challenging many of our assumptions regarding the behavior of mammary stem cells, and we show how understanding these cellular lineages has altered our view of breast cancer.