Final Report Summary - REPROL53U48 (Characterization of direct reprogramming-regulating factors LIN-53 and USP-48.)
Studying cell type conversion in model organisms can provide insight into mechanisms that maintain and protect cellular identities. Knowledge about such mechanisms has the potential to facilitate cell fate reprogramming strategies thereby supporting the development of future biomedical approaches such as tissue replacement therapies. The direct conversion of mature somatic cells to a different cell type by ectopically expressed fate-inducing Transcription Factors (TFs) is a promising strategy to generate required tissues in vivo. Although direct conversion, also known as transdifferentiation, has been successfully applied in some cases, it appears that most cell types cannot be efficiently transdifferentiated by forced expression of specific TFs.
Recent studies provide evidence that inhibitory mechanisms play an important role in restricting cellular reprogramming. Such inhibitory mechanisms are often conveyed by factors that regulate accessibility to chromatin through modifying histones or remodeling chromatin structures. Yet, it is not well understood, which factors act as barriers for cellular reprogramming and importantly, whether they act the same way in different tissues and species.
Baris Tursun’s group is using C. elegans as an in vivo genetic model system to identify cell fate reprogramming barriers. By applying large-scale forward and reverse genetic screenings with high-throughput techniques his group identified factors involved in inhibiting the induction of neuronal or muscle fates in different tissue types. Previously, Tursun and colleagues have shown that the histone chaperone LIN-53 (Caf1p48/Rbbp7 in mammals) (Tursun et al., Science 2011) acts as a barrier for converting germ cells into specific neurons or muscle cells. They further revealed that LIN-53 acts together with PRC2 (Polycomb Repressive Complex 2) in germ cells and his group discovered that Notch signaling counteracts LIN-53 and PRC2-mediated chromatin silencing (Patel et al., Cell Reports 2012; Seelk et al. Elife 2016).
Moreover, LIN-53 acts with the NuRD chromatin-remodeling complex in order to maintain muscular integrity. The findings provided by the Tursun group might facilitate tissue replacement therapies, which could help patients suffering from degenerative diseases such as Parkinson’s, Alzheimer’s and Muscular Dystrophy.
The independent research group of Baris Tursun at the Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association comprises six PhD students, one postdoc and two technicians. As the Principal Investigator (PI) and group leader Baris Tursun has been awarded the ERC-Starting-Grant in December 2014, which is in effect since early 2015. Baris Tursun’s position at the Max Delbrück Center (MDC) has been extended allowing him to continue the mission of his group to identify mechanisms that safeguard cells and thereby antagonize cell fate reprogramming.
Recent studies provide evidence that inhibitory mechanisms play an important role in restricting cellular reprogramming. Such inhibitory mechanisms are often conveyed by factors that regulate accessibility to chromatin through modifying histones or remodeling chromatin structures. Yet, it is not well understood, which factors act as barriers for cellular reprogramming and importantly, whether they act the same way in different tissues and species.
Baris Tursun’s group is using C. elegans as an in vivo genetic model system to identify cell fate reprogramming barriers. By applying large-scale forward and reverse genetic screenings with high-throughput techniques his group identified factors involved in inhibiting the induction of neuronal or muscle fates in different tissue types. Previously, Tursun and colleagues have shown that the histone chaperone LIN-53 (Caf1p48/Rbbp7 in mammals) (Tursun et al., Science 2011) acts as a barrier for converting germ cells into specific neurons or muscle cells. They further revealed that LIN-53 acts together with PRC2 (Polycomb Repressive Complex 2) in germ cells and his group discovered that Notch signaling counteracts LIN-53 and PRC2-mediated chromatin silencing (Patel et al., Cell Reports 2012; Seelk et al. Elife 2016).
Moreover, LIN-53 acts with the NuRD chromatin-remodeling complex in order to maintain muscular integrity. The findings provided by the Tursun group might facilitate tissue replacement therapies, which could help patients suffering from degenerative diseases such as Parkinson’s, Alzheimer’s and Muscular Dystrophy.
The independent research group of Baris Tursun at the Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association comprises six PhD students, one postdoc and two technicians. As the Principal Investigator (PI) and group leader Baris Tursun has been awarded the ERC-Starting-Grant in December 2014, which is in effect since early 2015. Baris Tursun’s position at the Max Delbrück Center (MDC) has been extended allowing him to continue the mission of his group to identify mechanisms that safeguard cells and thereby antagonize cell fate reprogramming.