Exploring blastema heterogeneity during salamander limb regeneration
Ahmed Elewa1, Ilgar Abdullayev2, Åsa K Bjorklund3, Thomas Hauling4, Heng Wang1, Åsa Segerstolpe2, Raquel Firnkes5, Connie Xu6, Nuria Oliva Vilarnau7, Mats Nilsson4, Rickard Sandberg2, Andras Simon1
1Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden;
2Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden and Ludwig Institute for Cancer Research, Stockholm, Sweden; 3Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden; 4Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Tomtebodavägem 23A, 17165, Solna, Sweden; 5Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden and Master's Program in Nutrition, Karolinska Institute/Stockholm University, Sweden
6Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden and Master’s Programme in Biomedicine, Karolinska Institute, Sweden;7Department of Cell and Molecular Biology, Karolinska Institute, Solna, Sweden and Biomedicine Master Program, Lund University, Lund, Sweden
Salamanders display an impressive ability to regenerate lost body parts, including complete restoration of lost limbs. Central to this process is the formation of a blastema; an autonomous mass of histologically indistinguishable cells that develop into the new appendage. Historically, the blastema has been described as a mass of dedifferentiated cells. However, recent studies have begun to challenge this generalization. For example, what is the contribution of resident stem cells to the blastema? What is the extent of dedifferentiation and to what extent do dedifferentiated cells remain committed to their lineage of origin? We set out to address these questions by combining single-cell RNA-seq and padlock in situ sequencing of the regenerating newt limb. Our results provide unprecedented insight into blastema heterogeneity during limb regeneration and provide the information necessary to develop blastema specific expression markers.
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