The role of Isl1-mediated transcriptional regulation and asymmetric cell division in fate decisions of cardiac progenitor cells

• Applicant: Professorin Dr. Gergana Dobreva
• Subject Area: Cardiology, Angiology
• Term: from 2007 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 52609373

Stem (progenitor) cells possess the unique capacity to either self-renew through cell division or to differentiate into a variety of specialized daughter cells, which are necessary both for embryonic organogenesis and for tissue regeneration. The heart is formed by two populations of progenitor cells. During embryogenesis, the first population gives rise to the left ventricle, while the second one generates the right ventricle, the outflow tract and parts of the atria. The LIM-homeodomain transcription factor Isl1 marks the second population of cardiac progenitors, but little is known about the downstream targets of Isl1 during heart development. The aim of this research program is to identify Isl1 downstream target genes and to characterize the nature of the cardiac-specific Isl1-containing transcriptional complex. This will provide a basis to further elucidate the mechanisms responsible for Isl1-dependent heart specific gene regulation in the context of the three-dimensional chromatin environment. In addition, we would like to determine whether asymmetric cell division plays a role in the multipotent Isl1+ cardiovascular progenitors for the choice between self-renewal and adopting differentiated fates. We expect that this work will shed light on the molecular mechanisms of cardiac progenitor maintenance, lineage specification and differentiation.

• DFG Programme: Independent Junior Research Groups