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- Coronal brain atlas in stereotaxic coordinates of the African spiny mouse, acomys cahirinusPublication . Vitorino, Marta; S, Simão; Moreira, João B.; Nogueira‐Rodrigues, Joana; Silva, Joana A; Sofia Lourenço, Ana; Vitor Fernandes, Dr; Sousa, Monica M.; Tiscornia, Gustavo; Araújo, Inês MariaThe African spiny mouse (Acomys cahirinus) is an emerging model of mammalian epimorphic regeneration that has aroused the interest of the scientific community in the last decade. To date, studies on brain repair have been hindered by the lack of knowledge on the neuroanatomy of this species. Here, we present a coronal brain atlas in stereotaxic coordinates, which allows for three-dimensional identification and localization of the brain structures of this species. The brain of 12-week-old spiny mice was mapped in stereotaxic coordinates using cresyl violet-stained brain sections obtained from coronal cryosectioning of the brain after transcardial perfusion with fixative. The atlas is presented in 42 plates representing sections spaced 240 mu m apart. Stereotaxic coordinates were validated using both a model of Parkinsonian lesion of the striatum with 6-hydroxydopamine and labeling of the corticospinal tract in the spiny mouse spinal cord using AAV1/2-GFP intracortical injections. This work presents a new tool in A. cahirinus neurobiology and opens new avenues of research for the investigation of the regenerative ability of A. cahirinus in models of brain disorders.
- Human oocyte meiotic maturation is associated with a specific profile of alternatively spliced transcript isoformsPublication . Cornet‐Bartolomé, David; Barragán, Montserrat; Zambelli, Filippo; Ferrer‐Vaquer, Anna; Tiscornia, Gustavo; Balcells, Susanna; Rodriguez, Amelia; Grinberg, Daniel; Vassena, RitaThe transition from a transcriptionally active state (GV) to a transcriptionally inactive state (mature MII oocytes) is required for the acquisition of oocyte developmental competence. We hypothesize that the expression of specific genes at the in vivo matured (MII) stage could be modulated by posttranscriptional mechanisms, particularly regulation of alternative splicing (AS). In this study, we examined the transcriptional activity of GV oocytes after ovarian stimulation followed by oocyte pick-up and the landscape of alternatively spliced isoforms in human MII oocytes. Individual oocytes were processed and analyzed for transcriptional activity (GV), gene expression (GV and MII), and AS signatures (GV and MII) on HTA 2.0 microarrays. Samples were grouped according to maturation stage, and then subgrouped according to women's age and antral follicular count (AFC); array results were validated by quantitative polymerase chain reaction. Differentially expressed genes between GV and MII oocytes clustered mainly in biological processes related to mitochondrial metabolism. Interestingly, 16 genes that were related to the regulation of transcription and mitochondrial translation showed differences in alternatively spliced isoform profiles despite not being differentially expressed between groups. Altogether, our results contribute to our understanding of the role of AS in oocyte developmental competence acquisition.
- Trophoblast attachment to the endometrial epithelium elicits compartment-specific transcriptional waves in an in-vitro modelPublication . Vergaro, Paula; Tiscornia, Gustavo; Zambelli, Filippo; Rodríguez, Amelia; Santaló, Josep; Vassena, RitaImplantation is a major bottleneck in human reproduction (Polanski et al., 2014). The average implantation rate for an embryo ranges from 30% to 40% (Coughlan et al., 2014). Recurrent implantation failure (RIF) is estimated to occur in approximately 4% of IVF cycles (Koot et al., 2012), although estimates vary because there are several somewhat different definitions of RIF in the literature. Implantation of the blastocyst in the receptive endometrium is a sequential process involving apposition, attachment and invasion that precedes the establishment of pregnancy (Wang and Dey, 2006). Successful implantation requires embryo competence and endometrial receptivity, both of which are dynamic and highly regulated states (Wang and Dey, 2006). In addition to genetic disorders (which are a major cause of implantation failure and miscarriage), embryo competence, quality and ultimately developmental potential depend on the embryo achieving the correct regulatory, signalling and metabolic states (Fu et al., 2009; Hourvitz et al., 2006; Lundin et al., 2001; Simon and Laufer, 2012; Sjoblom et al., 2006). A key determinant of these embryonic states is their underlying transcriptional dynamics; for instance, waves of embryonic transcriptional activation direct early development and the symmetry breaking needed for cell fate specification (Shi et al., 2015; Vassena et al., 2011).
- Matrisomal components involved in regenerative wound healing in axolotl and acomys: implications for biomaterial developmentPublication . Avila-Martinez, Nancy; Gansevoort, Merel; Verbakel, Juul; Jayaprakash, Haarshaadri; Araujo, Ines; Vitorino, Marta; Tiscornia, Gustavo; van Kuppevelt, Toin H.; Daamen, Willeke F.Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (Ambystoma mexicanum) are capable of regenerating whole organs and even limbs, most mammals heal their wounds via fibrotic scarring. Recently, the African spiny mouse (Acomys sp.) has been shown to be injury resistant and capable of regenerating several tissue types. A major focal point of research with Acomys has been the identification of drivers of regeneration. In this search, the matrisome components related to the extracellular matrix (ECM) are often overlooked. In this review, we compare Acomys and axolotl skin wound healing and blastema-mediated regeneration by examining their wound healing responses and comparing the expression pattern of matrisome genes, including glycosaminoglycan (GAG) related genes. The goal of this review is to identify matrisome genes that are upregulated during regeneration and could be potential candidates for inclusion in pro-regenerative biomaterials. Research papers describing transcriptomic or proteomic coverage of either skin regeneration or blastema formation in Acomys and axolotl were selected. Matrisome and GAG related genes were extracted from each dataset and the resulting lists of genes were compared. In our analysis, we found several genes that were consistently upregulated, suggesting possible involvement in regenerative processes. Most of the components have been implicated in regulation of cell behavior, extracellular matrix remodeling and wound healing. Incorporation of such pro-regenerative factors into biomaterials may help to shift pro-fibrotic processes to regenerative responses in treated wounds.