Mouse embryonic stem cell lines were derived three decades ago and allow the process of transgenesis and in turn the generation of transgenic mice. In the past and still nowadays, these mice as well as more primitive organisms have provided models to study the first cell decisions in the embryo. Derivation of human embryonic stem cells more than a decade ago has provided a similar cell model for human early embryonic development, an issue that could not be addressed for obvious ethical reasons which limit research on human embryos. These cells allow investigating the genetic and epigenetic mechanisms underlying the first cell decisions in the human embryo. Herein, we use cardiogenesis as an example to reveal the potential of these cells to better understand the first steps of cardiac development.

Progresses in pediatric oncology over the last decades have been dramatic and allow current cure rates above 80%. There are mainly due to multicentre clinical trials aiming at optimizing chemotherapy protocols as well as local therapies in a stepwise approach. Most of the new anticancer drugs currently in development are based on targeted therapies, directed to specific targets present only in or on tumor cells, like growth factor receptors, mechanisms involved in proliferation, DNA repair, apoptosis, tumor invasion or angiogenesis. Concerning bone marrow transplantation also, new strategic approaches are in advanced development. They aim at reducing treatment induced toxicity and enhancing efficacy at the same time. This short paper would like to point out these new technologies, which should be known by the general practitioner.

Primary cicatricial alopecias (PCA) result from the inflammatory destruction of the hair follicle, followed by its replacement by a fibrotic streamer. The involvement of multipotent stem cells of the hair follicle is possible through a transdifferentiation pathway. The diagnosis relies on clinico-pathologic correlations. PCA are classified as the neutrophilic, lymphocytic and mixed types. Each of these groups gather specific disorders including folliculitis decalvans, dissecting folliculitis of the scalp, erosive pustulosis of the scalp, keloidal acne of the nape, frontal fibrosing alopecia, lichen planopilaris and lupus erythematosus.

The onset of metastasis is a critical event in the natural history of cancer, and is generally associated with a poor clinical outcome. Mechanistically, the metastatic process is made of several steps that are biologically distinct and now rather well characterized. Several explanatory models have been proposed: selective models (clonal selection), adaptive models (initial oncogenesis), involvement of tumor "stem" cells, epithelial-mesenchymal transition… The next progresses are expected to come from the characterization of circulating and disseminated tumor cells, which are two recently opened windows on the metastatic process in patients.

Childhood cancers account for 1% of malignant tumors. As a result of advances in treatment, almost 80% of children and adolescents who currently receive a diagnosis of cancer become long-term survivors. Assessment of potential for fertility preservation should thus be a systematic element of care for children treated for a malignant tumor (high-dose chemotherapy with alkylizing agents, radiation therapy including the gonads) or those receiving hematopoietic stem cell grafts for malignant or benign disease (sickle-cell anemia, immune deficit). Potential adverse consequences of treatment include impaired puberty and fertility due to gonadal removal, genital tract injury or damage to germ cells from adjuvant therapy. Advances in assisted reproductive technologies have led to new possibilities for the prevention and treatment of infertility. Among them, cryopreservation of ovarian tissue appears to be the most promising, or perhaps the only one available before puberty with encouraging results. Nevertheless the uncertainties, or even risks, related to these treatments, should not be neglected. We review experimental data in mouse and sheep animal models. The results demonstrate that immature ovarian grafting can restore spontaneous puberty and fertility in both models. This study addresses the very important issue of epigenetics, and provides valuable information for the study of ovarian transplantation, suggesting that these procedures do not perturb normal epigenetic marks. These results are highly relevant to the question of immature cortex reimplantation.

Sézary syndrome (SS) represents 3% of cutaneous T-cell lymphomas (CTCL). It is an aggressive epidermotropic CTCL with a 5-year survival rate of 24%. According to EORTC (European organization for research and treatment of cancer), SS is defined by erythroderma, diffuse lymphadenopathy, atypical T lymphocytes (>1000/mm(3)), and the presence of a major blood, cutaneous and nodal T cell clone. A specific marker for atypical tumoral T lymphocytes known as Sézary cells was identified in 2001, namely KIR3DL2 (CD158k) receptor, which allows more specific diagnosis of SS; levels of this marker are highly correlated with the clinical course of the disease. In therapeutic terms, clinical trials are being conducted on new molecules that point towards an improved prognosis for this disease. We propose a review of Sézary syndrome, which is currently the subject of scientific papers concerning both physiopathology and therapeutics, with new prospects of targeted therapy.

One of the major advance concerning skin carcinoma is the development of targeted therapy: anti-patch/sonic/hedgehog for basal cell carcinoma (BCC) and anti-EGFR for squamous cell carcinoma (SCC). These therapies are indicated for advanced non surgically removable tumors. Their anti-tumoral efficacy has been shown, their effect seems to be suspensive which raises the question of their tolerability for long term use. Laboratory work have shown that BCC and SCC stem cells locate in different cell compartments and follow distinct molecular events which explains their distinct behaviour. The role of HPV in EBDR skin cancers has been ruled out. Photodynamic therapy induced-immunosuppression can be prevented by lowering the light fluence. The gene responsible for the Ferguson Smith syndrome has been identified: it is the gene encoding TGFBR1. Its implication in SCC needs to be determined. A new compound, PEP005, (ingenol mebutate) should soon enlarge therapeutical options for actinic keratosis. Concerning melanoma, results of the two phase III studies using two innovative therapies (anti-Braf and ipilimumab) have been published. Comparative study between anti-Braf and DTIC has shown a response rate of 48.4 % with vemurafenib and 5.5 % with DTIC. The risk of death was diminished by 67 %. These results have allowed to switch to vemurafenib patients with progression under DTIC. However, the initial response is followed by relapse in a majority of cases. Mechanisms of this resistance have been studied and the inhibition of several molecules involved in different or identical pathway should help to resolve that problem. The combination ipilimumab+ DTIC gives better results than DTIC alone. The adverse events of this association are slightly different than those seen with ipilimumab alone. They must be known by prescribers. Some discussions are on their way between the two companies developping anti-Braf and ipilimumab to develop therapeutic strategies combining both treatments. 20 to 30 % of patients taking anti-Braf drugs will develop SCC (due to paradoxal activation of MAPK in non Braf mutated cells). PEG-interferon seems to be indicated in ulcerated melanoma with lymph node micrometastasis. Some other targeted molecules such as C-KIT and anti-MEK are under evaluation. The effect of sunscreens on melanoma risk prevention has been reported in an Australian study. A low vitamine D status is reported to have a bad prognosis in melanoma and is observed in fair skin patients at risk. Recommendations for the care and follow up of patients with Merkel carcinoma have been published. The elevated risk of positive sentinel lymph nodes in these patients does not allow to define a subgroup of Merkel patients that could be spared from the technique. Sarcoma also benefit from targeted therapy especially DFSP with imatinib. Other molecules among which mTOR inhibitors are being evaluated in sarcomas. A collaborative work has allowed to classify and evaluate in a more standardized way cutaneous T lymphomas and should help future trials. Some microRNA can be used as diagnostic tools or therapies in T cell cutaneous lymphomas. Finally a review of modern therapeutical strategies in cutaneous lymphomas has been published.

Dermatological research has been very active this year. Most of the numerous fields investigated involve the mechanisms of cutaneous regeneration and barrier function. A novel target of early ultraviolet-induced skin photodamage, the Syk kinase, has been recently identified. Synergistic relationship between telomere damage and cutaneous progerin production during cell senescence may also participate in the natural skin aging process. Interestingly, ultraviolet radiation induces an inhibitory effect on subcutaneous lipogenesis. Androgenetic alopecia or common baldness is not characterized by loss of hair follicle stem cells but by a defect in the conversion of hair follicle stem cells into active progenitor cells. It has been shown that the cornified envelope functions not only as a physicomechanical barrier, but also as both a biochemical line of antoxidant defense and an immunological line of defense. Like human papillomaviruses, Merckel cell polyomavirus belongs to the skin microbiome and different studies have demonstrated the protective role of epidermal resident microflora through the activation of innate immunity. Production of antimicrobial peptides and the activation of inflammasome and plasmacytoid dendritic cells are involved in the modulation of the cutaneous barrier function. Results from different studies suggest that IL-22 and IL-36 may be common mediators of both innate and adaptive immune responses. All these pathways interact not only to maintain cutaneous homeostasis and integrity (wound healing) but also to regulate autoinflammatory and autoimmune dermatoses (psoriasis, lupus, rosacea, atopic dermatitis, etc...). In addition, molecular mechanisms that regulate T helper type 2 differentiation and the retention at the site of inflammation of Th2 cells have been identified. New promising therapeutic targets for different chronic dermatosis are thus suggested. Mechanobiology and mechanotransduction are also emerging fields that investigate mechanical interactions between living cells and their environment and the conversion of mechanical cues into biochemical signals. Electronic second skin is now a current concept through bio-integrated epidermal electronics platforms used for different monitoring and stimulations of body functions.

Since the end of 2010, France by "l'Agence de Biomédecine" has validated the embryo vitrification procedure as an improvement of the slow freezing method. We presented here data concerning biological and clinical outcomes from a prospective observational study where early cleavage stage good quality embryos were vitrified and warmed. We compared these results to those of a retrospective series where embryos were thawed after a slow freezing procedure (SF). We report also the first French live birth following embryo vitrification.

Cancer is a multi-etiologic, multistage disease with a prevalent genetic component, which happens when a large number of genes, critical for cell growth, death, differentiation, migration, and metabolic plasticity are altered irreversibly, so as to either "gain" (oncogenes) or "lose" (tumour suppressors) their function. Recent discoveries have revealed the previously underestimated etiologic importance of multiple epigenetic, that is to say, reversible factors (histone modifications, DNA methylation, non-coding RNA) involved in the transcriptional and post-transcriptional regulation of proteins, indispensable for the control of cancerous phenotype. Stable alterations of epigenetic machinery ("epimutations") turn out to play a critical role at different steps of carcinogenesis. In addition, due to substantial recent progress in stem cell biology, the new concept of cancer stem cells has emerged. This, along with newly discovered epigenetic cancer mechanisms, gives rise to a hope to overcome radio- and chemo-resistance and to eradicate otherwise incurable neoplasms.

Severely burned patients need effective and permanent wound coverage. The outcome of massive burn injuries has improved with the use of cultured epithelial autografts (CEA), despite their fragility, frequent failure to take, high cost and long-term tendency to contract. Combining CEA with dermal substitutes provides earlier skin closure and satisfactory functional results. Another promising line of research is skin regeneration with epidermal stem cells, which have the capacity to differentiate into keratinocytes, to promote wound repair, and to regenerate skin appendages. Human mesenchymal stem cells have been evaluated in radiation-induced skin damage.

Even if major progress has been made in the medical treatment for pituitary adenomas in the last decades, currently available drugs do not always control hormonal secretion of these tumors. New molecules or new formulations of old drugs are under development. Pituitary stem cells research is currently also very active.

Hematopoietic stem cells (HSC) are the source of all blood cell types produced during the entire life of an organism. They appear during embryonic development, where they will transit through different successive hematopoietic organs, before to finally colonize the bone marrow. Nowadays, the precise origin of HSC remains a matter of controversy. Different HSC precursor candidates, located in different anatomical sites, have been proposed. Here, we summarize and discuss the different theories in light of the recent articles, especially those using in vivo confocal microscopy technology.