Project description:The inner cell mass in blastocyst is the origin of all the somatic and germ cells in mammals, and of pluripotent stem cells in vitro. As the conserved principles between pig and human, here we performed comprehensive single-cell RNA-seq for porcine early embryos from oocyte to early blastocyst. We show the specification of inner cell mass and trophectoderm in morula, and the molecular signature of the precursors. We demonstrate the existence of naïve pluripotency signature in morula and inner cell mass of early blastocyst, and the specific pluripotent genes and the activity of signalling pathways highlight the characteristics of the naïve pluripotency. We observe absence of dosage compensation with respect to X-chromosome in morula, and incomplete dosage compensation in early blastocyst. However, the dynamics of dosage compensation may be independent on the expression of XIST induced X-chromosome inactivation. Our study describes molecular landmarks of embryogenesis in pig that will provide a better strategy for derivation of porcine pluripotent stem cells and improve the research in regenerative medicine.
Project description:Gene expression analysis of early thymic progenitors and thymus seeding progenitors Eight distinct populations were analysed, each with between 2 and 6 biological replicates.
Project description:Tumor heterogeneity resulting from clonal evolution is a frequent feature in clear cell renal cell carcinoma (ccRCC) and could play a role in metastatic dissemination. However, the dynamics of metastatic evolution is not completely elucidated and could follow a complex seeding process. Using a unique experimental design with a rare matched primary-metastatic case prior to any medical treatment, we retraced the lineage of metastatic clones that showed a complex, multiple, polyphyletic seeding of two functionally interdependent subclonal populations originating from the primary tumor, in the direction of all metastatic sites.
Project description:Tumor heterogeneity resulting from clonal evolution is a frequent feature in clear cell renal cell carcinoma (ccRCC) and could play a role in metastatic dissemination. However, the dynamics of metastatic evolution is not completely elucidated and could follow a complex seeding process. Using a unique experimental design with a rare matched primary-metastatic case prior to any medical treatment, we retraced the lineage of metastatic clones that showed a complex, multiple, polyphyletic seeding of two functionally interdependent subclonal populations originating from the primary tumor, in the direction of all metastatic sites.
Project description:Development of T lymphocytes in the thymus has been widely studied in mice, but our insights into human T cell development are scarce. Using a combination of single-cell techniques and functional assays, we report deep immune profiling of human T cell development, with a focus on the initial development stages of pre-lineage commitment. We identified three thymus-seeding progenitor populations that also have a counterpart in the bone marrow. We found that the human thymus physiologically supports development of monocytes, DCs, NK cells, and limited development of B lymphocytes. These insights are important to monitor and guide regenerative therapies after hematopoietic stem cell transplantation.
Project description:The maternal tract plays a critical role in the success of early embryonic development providing an optimal environment for establishment and maintenance of pregnancy. Preparation of this environment requires an intimate dialogue between the embryo and her mother. To advance our understanding of the process by which a foreign blastocyst is accepted by the maternal endometrium and better address the clinical challenges of infertility and pregnancy failure, it is imperative to decipher this complex molecular dialogue. The objective of the present work is to define the local response(s) of the maternal tract towards the embryo during the earliest stages of pregnancy. In order to identify the uterine gene expression modified in the presence of the embryo when compared to the oocyte we used a novel model that eliminated genetic variability. Using laparoscopic insemination one oviduct was inseminated with spermatozoa and the contralateral oviduct was injected with diluent. This model allowed us to obtain samples from the oviduct and the uterine horn containing either embryos or oocytes from the same sow. Uterine horn pig samples containing embryos at blastocyst stage and and their contralateral uterine horn containing oocytes from individual sows were collected for RNA isolation and hybridization on Affymetrix microarrays. Three biological replicates were performed (n= 3 sows) and a total of 6 arrays were used for microarrays study (3 arrays for uterine horn samples containing embryos (inseminated-side) and 3 arrays for samples containing oocytes (non-inseminated side).