Transcription factors and the control of Stem Cell functions The development of complex organs and tissues, such as brain and the hematopoietic system, requires the ordered expression of key transcription factors controlling cell type- and tissue-specific gene expression. Stem cells represent the self renewing compartment of rapidly replicating cell types, as in the hematopoietic system, but are present, in small numbers, also in adult brain, heart and other organs which do not show active cell replication in adults.
The Genetics Group in the Dipartimento di Biotecnologie e Bioscienze (S.O., S. Nicolis and A.Ronchi) use a common set of approaches (conditional and standard targeted mutagenesis in mouse, cell culture and gene transduction, chromatin studies, etc.) to investigate the role of key transcription factors in the development, maintenance and differentiation of a variety of stem cells.
In particular, we ( S.O.) identified, using transgenic constructs, a subset of c-kit genomic sequences which drive expression of a reporter gene in Primordial Germ Cells, and some of their descendants, as well as in Hematopoietic Stem Cells and early progenitors. Using Chromatin Immunoprecipitation and other techniques (3C assay) we are trying to define transcription factors interacting with the main regulatory areas of the gene (with B. Gottgens, Cambridge). The regulation of the same transgene is also being studied in embryonic stem cells and in spermatogonia (with S. Dolci, Univ. Roma 2).
GFP expression driven by the same transgene is also used to track stem cells migrating from the bone marrow to the heart, and to test their ability to develop in vitro as cardiac stem cells (with E. Messina, Roma and C. Magli, CNR, Pisa).
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