Dataset Information

Stemness Activity Underlying Whole Brain Regeneration in a Basal Chordate.

ABSTRACT: Understanding how neurons regenerate following injury remains a central challenge in regenerative medicine. Adult mammals have a very limited ability to regenerate new neurons in the central nervous system (CNS). In contrast, the basal chordate Polycarpa mytiligera can regenerate its entire CNS within seven days of complete removal. Transcriptome sequencing, cellular labeling, and proliferation in vivo essays revealed that CNS regeneration is mediated by a newly formed neural progeny and the activation of neurodevelopmental pathways that are associated with enhanced stem-cell activity. Analyzing the expression of 239 activated pathways enabled a quantitative understanding of gene-set enrichment patterns at key regeneration stages. The molecular and cellular mechanisms controlling the regenerative ability that this study reveals can be used to develop innovative approaches to enhancing neurogenesis in closely-related chordate species, including humans.

SUBMITTER: Gordon T

PROVIDER: S-EPMC9738451 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stemness Activity Underlying Whole Brain Regeneration in a Basal Chordate.

Gordon Tal T Zaquin Tal T Kowarsky Mark Alec MA Voskoboynik Yotam Y Hendin Noam N Wurtzel Omri O Caicci Federico F Manni Lucia L Voskoboynik Ayelet A Shenkar Noa N

Cells 20221122 23

Understanding how neurons regenerate following injury remains a central challenge in regenerative medicine. Adult mammals have a very limited ability to regenerate new neurons in the central nervous system (CNS). In contrast, the basal chordate <i>Polycarpa mytiligera</i> can regenerate its entire CNS within seven days of complete removal. Transcriptome sequencing, cellular labeling, and proliferation in vivo essays revealed that CNS regeneration is mediated by a newly formed neural progeny and ...[more]

PMID: 36496987

Similar Datasets

Project description:BackgroundUnidirectional regeneration in the basal chordate Ciona intestinalis involves the proliferation of adult stem cells residing in the branchial sac vasculature and the migration of progenitor cells to the site of distal injury. However, after the Ciona body is bisected, regeneration occurs in the proximal but not in the distal fragments, even if the latter include a part of the branchial sac with stem cells. A transcriptome was sequenced and assembled from the isolated branchial sacs of regenerating animals, and the information was used to provide insights into the absence of regeneration in distal body fragments.ResultsWe identified 1149 differentially expressed genes, which were separated into two major modules by weighted gene correlation network analysis, one consisting of mostly upregulated genes correlated with regeneration and the other consisting of only downregulated genes associated with metabolism and homeostatic processes. The hsp70, dnaJb4, and bag3 genes were among the highest upregulated genes and were predicted to interact in an HSP70 chaperone system. The upregulation of HSP70 chaperone genes was verified and their expression confirmed in BS vasculature cells previously identified as stem and progenitor cells. siRNA-mediated gene knockdown showed that hsp70 and dnaJb4, but not bag3, are required for progenitor cell targeting and distal regeneration. However, neither hsp70 nor dnaJb4 were strongly expressed in the branchial sac vasculature of distal fragments, implying the absence of a stress response. Heat shock treatment of distal body fragments activated hsp70 and dnaJb4 expression indicative of a stress response, induced cell proliferation in branchial sac vasculature cells, and promoted distal regeneration.ConclusionsThe chaperone system genes hsp70, dnaJb4, and bag3 are significantly upregulated in the branchial sac vasculature following distal injury, defining a stress response that is essential for regeneration. The stress response is absent from distal fragments, but can be induced by a heat shock, which activates cell division in the branchial sac vasculature and promotes distal regeneration. This study demonstrates the importance of a stress response for stem cell activation and regeneration in a basal chordate, which may have implications for understanding the limited regenerative activities in other animals, including vertebrates.

Dataset Information

Stemness Activity Underlying Whole Brain Regeneration in a Basal Chordate.

Publications

Stemness Activity Underlying Whole Brain Regeneration in a Basal Chordate.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets