scholarly journals Conservation of EMT transcription factor function in controlling pluripotent adult stem cell migration in vivo in planarians

2016 ◽  
Author(s):  
Prasad Abnave ◽  
Ellen Aboukhatwa ◽  
Nobuyoshi Kosaka ◽  
James Thompson ◽  
Mark A. Hill ◽  
...  

SUMMARYMigration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infections. Inappropriate migration also underpins the formation of metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in the planarians. We demonstrate that we can use this system to study the molecular control of stem cell migration and show that snail and zeb-1 EMT transcription factors homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. Our work establishes planarians as a suitable model for further in depth study of the processes controlling stem cell migration in vivo.

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Sounak Sahu ◽  
Divya Sridhar ◽  
Prasad Abnave ◽  
Noboyoshi Kosaka ◽  
Anish Dattani ◽  
...  

Mechanical stress during cell migration may be a previously unappreciated source of genome instability, but the extent to which this happens in any animal in vivo remains unknown. We consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and exhibit increased levels of DNA damage. Increased DNA damage levels reduce once stem cells reach the wound site. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration and migrating stem cell populations are more sensitive to further DNA damage than stationary stem cells. RNAi mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that active DNA repair pathways are required to allow successful migration to a distal wound site. Together these findings provide evidence that levels of Migration-Coupled-DNA-Damage (MCDD) are significant in adult stem cells and that ongoing migration requires DNA repair mechanisms. Our findings reveal that migration of normal stem cells in vivo represent an unappreciated source of damage, that could be a significant source of mutations in animals during development or during long term tissue homeostasis.


2019 ◽  
Author(s):  
Sounak Sahu ◽  
Divya Sridhar ◽  
Prasad Abnave ◽  
Nobuyoshi Kosaka ◽  
Anish Dattani ◽  
...  

AbstractThe impact of mechanical stress during cell migration may be a previously unappreciated source of genome instability [1–3], but to what extent this happens in vivo remains unknown. Here we consider an in vivo system where the adult stem cells of planarian flatworms are required to migrate to a distal wound site [4]. We observe a relationship between adult stem cell migration and ongoing DNA damage and repair during tissue regeneration. Migrating planarian stem cells undergo changes in nuclear shape and increased levels of DNA damage. Increased DNA damage levels resolve once stem cells reach the wound site and stop migrating. Stem cells in which DNA damage is induced prior to wounding take longer to initiate migration suggesting migration activity is sensitive to DNA damage. Migrating stem cells populations are more sensitive to further DNA damage than stationary stem cells, providing evidence that levels of migration-coupled-DNA-damage (MCDD) are significant. RNAi mediated knockdown of DNA repair pathway components blocks normal stem cell migration, confirming that DNA repair pathways are required to allow successful migration to a distal wound site. Together these lines of evidence demonstrate that migration leans to DNA damage in vivo and requires DNA repair mechanisms. Our findings reveal that migration of stem cells represents an unappreciated source of damage, that could be a significant source of mutations in animals during development or during long term tissue homeostasis.


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S692-S692
Author(s):  
Mathias Hoehn ◽  
Uwe Himmelreich ◽  
Ralph Weber ◽  
Pedro Ramos-Cabrer ◽  
Susanne Wegener ◽  
...  

2010 ◽  
Vol 211 (3) ◽  
pp. S93
Author(s):  
Dustin M. Bermudez ◽  
Benjamin J. Herdrich ◽  
David Stitelman ◽  
Antoneta Radu ◽  
Haiying Li ◽  
...  

2019 ◽  
Vol 20 (5) ◽  
pp. 1118 ◽  
Author(s):  
Jordi Camps ◽  
Hanne Grosemans ◽  
Rik Gijsbers ◽  
Christa Maes ◽  
Maurilio Sampaolesi

Progressive muscle degeneration followed by dilated cardiomyopathy is a hallmark of muscular dystrophy. Stem cell therapy is suggested to replace diseased myofibers by healthy myofibers, although so far, we are faced by low efficiencies of migration and engraftment of stem cells. Chemokines are signalling proteins guiding cell migration and have been shown to tightly regulate muscle tissue repair. We sought to determine which chemokines are expressed in dystrophic muscles undergoing tissue remodelling. Therefore, we analysed the expression of chemokines and chemokine receptors in skeletal and cardiac muscles from Sarcoglycan-α null, Sarcoglycan-β null and immunodeficient Sgcβ-null mice. We found that several chemokines are dysregulated in dystrophic muscles. We further show that one of these, platelet-derived growth factor-B, promotes interstitial stem cell migration. This finding provides perspective to an approachable mechanism for improving stem cell homing towards dystrophic muscles.


NeuroImage ◽  
2004 ◽  
Vol 21 (1) ◽  
pp. 311-317 ◽  
Author(s):  
Michel Modo ◽  
Karen Mellodew ◽  
Diana Cash ◽  
Scott E Fraser ◽  
Thomas J Meade ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ming-Siou Chen ◽  
Cheng-Yu Lin ◽  
Yun-Hsuan Chiu ◽  
Chie-Pein Chen ◽  
Pei-Jiun Tsai ◽  
...  

Mesenchymal stem cells (MSCs) are known for homing to sites of injury in response to signals of cellular damage. However, the mechanisms of how cytokines recruit stem cells to target tissue are still unclear. In this study, we found that the proinflammation cytokine interleukin-1β (IL-1β) promotes mesenchymal stem cell migration. The cDNA microarray data show that IL-1β induces matrix metalloproteinase-1 (MMP-1) expression. We then used quantitative real-time PCR and MMP-1 ELISA to verify the results. MMP-1 siRNA transfected MSCs, and MSC pretreatment with IL-1β inhibitor interleukin-1 receptor antagonist (IL-1RA), MMP tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), MMP-1 inhibitor GM6001, and protease-activated receptor 1 (PAR1) inhibitor SCH79797 confirms that PAR1 protein signaling pathway leads to IL-1β-induced cell migration. In conclusion, IL-1β promotes the secretion of MMP-1, which then activates the PAR1 and G-protein-coupled signal pathways to promote mesenchymal stem cell migration.


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