Projects / Programmes
Developmental potential of mammary gland cells: a comparative genomics approach
| Code |
Science |
Field |
Subfield |
| 4.06.03 |
Biotechnical sciences |
Biotechnology |
Animal biotechnology |
| Code |
Science |
Field |
| B000 |
Biomedical sciences |
|
| Code |
Science |
Field |
| 4.04 |
Agricultural and Veterinary Sciences |
Agricultural biotechnology |
mammary gland, stem cells, cell differentiation, cancer
Researchers (11)
Organisations (1)
Abstract
Background: Stem cells from different sources are widely used in biological basic and applied research. Stem cells play an important role in organ development and renewal, however, they are also often associated with tumorigenesis and cancer. Comparative genomic approach could reveal new basic regulatory mechnisms driving stem cell proliferation and differentiation. Mammary gland as an organ with cyclic charcter which undergoes several cycles of differentiation, proliferation and apoptosis during the female reproductive life appears to be also suitable as a model for stem cell studies. Scientific problem: Mammary gland is a highly specialized organ, responsible for milk synthesis. The existence of mammary stem cells has been inferred from reconstitution experiments where the entire functional mammary gland has been regenerated from tissue/cell transplants into the cleared murine mammary fat pad and from cytological studies in mouse, rat and humans. The presence of mammary stem/progenitor cells which drive development of differentiated mammary cell types is a basis for detailed study of the developmental potential of mammary stem cells (MaSC). However, their uneven distribution in the mammary gland offers the possibility to prove the concept of MaSC niche which includes the role of intercellular communication in the maintenance and renewal of the MaSC pool. Comparison of MaSCs from different species with an emphasis on cell signalling during the maintenance of the MaSc pool could be reveal important mechanisms, responsible for striking differences in occurrence of mammary cancer in different species. Comparison of transcriptomic data between species with high incidence of mammary cancer (human, mouse, dog) and those with virtually no cases of mammary cancer (cattle, goat, horse) could provide new insight into mechanisms triggering mammary cancer. The aim of the project is to confirm presence and developmental potential of MaSC in mouse, goat and cow using stem cell markers and to investigate their tumorigenic character. The identification of differences in developmental potential of MaSC from different species and their potential tumorigenic character could elucidate important mechanisms involved in renewal of mammary gland tissue and tumorigenesis. The comparative approach represents a novel strategy for identification of species specific MaSC expression profiles possibly related to tumorigenesis. The molecular background of mammary gland cancer in different species has not been sufficiently studied in the past, although it has the potential to reveal important regulatory mechanisms involved in cancer development. Methods: MaSC will be isolated from mammary glands of different species (mouse, cattle, goat, mare) and tested for expression of general and mammary gland stem cell markers. RNA sequencing, RT-PCR and immunohistochemistry will be used for gene expression studies and localisation of MaSCs in the mammary tissue. The developmental potential of MaSCs will be studied in mammary gland reconstitution model using transplantation in the cleared mouse mammary fat pad and their tumorigenic character will be tested using NOD/SCID mouse model. Relevance: The relevance of proposed research is supported with important questions in mammary gland development as well as with the suggested role of MaSC in mammary cancer. The differences among species may reveal important checkpoints in the differentiation process of the MaSC which could contribute to the identification of new candidates which are involved in triggering of mammary cancer. Organization and feasibility: experience in mammary gland and stem cell biology, availability of well equipped stem cell laboratory, collaboration at the international level with the laboratories working with stem cells (EADGENE NoE,) will allow exchange of materials and expertise necessary for realisation of the project.
Significance for science
The results of our research project are important because they shed light on the problem of identification of stem cells in the mammary gland, which are important from two different prospectives: they regulate regenerative potential of the mammary gland and are potentially the source for the development of tumors in the mammary gland. The comparative approach allows us to identify the common characteristics of stem cells in mammary gland, and opens the possibility to identify differences that lead to very different incidence of mammary tumors in different mammalian species. We expect that our results will allow monitoring of the localization of stem cells in the mammary gland and to obtain enriched populations of stem cells for detailed analysis of the transctiptome of the cells with the stem character.
Significance for the country
The topic of the project is relevant to better understand the course of lactation and gives the option of intervention in the development of the mammary gland. The comparative approach to the study stem cells from different species, however, provides an opportunity to identify risk factors that lead to the transition of stem cells into the tumor cells. The extension of the project in this direction could have implications for the diagnostics of mammary tumors in humans and thus the potential value to contribute to the improvement of public health.
Most important scientific results
Annual report
2010,
2011,
2012,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2010,
2011,
2012,
final report,
complete report on dLib.si
