Francesc Cebrià Lab

Planarian stem cells, the neoblasts, include truly pluripotent stem cells as well as a number of specialized neoblasts or lineage-committed progenitors from which all cell types differentiate. Thus, they offer an excellent model in which to study stem cell differentiation in vivo. However, very little is known about how pluripotent neoblasts specialize into lineage-committed progenitors and how these progenitors differentiate into their final mature types. In our laboratory we are interested in investigating the molecular and genetic pathways that regulate stem cell differentiation during planarian regeneration and homeostasis.

Contact

fcebrias@ub.edu

+93-4021499

Research

Stem cells maintenance and differentiation

EPIGENETIC REGULATION OF NEOBLAST DIFFERENTIATION

Epigenetic marks such as histone methylation and acetylation regulate the fate of stem cells by maintaining them in an undifferentiated state or triggering cell differentiation when required. However, little is known about the epigenetic regulation of planarian neoblasts. Is this epigenetic regulation conserved in these amazing animals? How does the epigenetic landscape change as neoblasts specialize into lineage-comitted progenitors first and mature cell types later? Our current approach is mainly focussed in understanding the role of the CREB-binding protein (CBP)/p300 family in the regulation of neoblast maintenance and differentiation. Members of this family are multi-functional proteins with histone acetyl-transferase activity that acetylate particular histone residues in order to regulate stem cell and progenitors differentiation in different models. Therefore, planarians offer us a model in which to study the epigenetic regulation of stem cells in vivo.

THE ROLE OF THE EGFR PATHWAY IN NEOBLAST DIFFERENTIATION

Signaling pathways play pivotal roles in triggering proper cell responses to extracellular signals. In the last years we have extensively characterized the function of the epidermal growth factor receptor (EGFR) signalling pathway in neoblast differentiation during planarian regeneration and homesotasis. Our laboratory has identified 10 putative EGF ligands and 6 EGF receptors that are expressed in different cell types. Whereas Smed-egfr-1 and Smed-nrg-1 are required for the final differentiation of gut progenitors into mature gut cells, Smed-egfr-4 seems to be required for the differentiation of eye progenitor into eye cels. These results suggest that in planarians the EGFR pathway could have a general role in the terminal differentiation of the distinct populations of lineage-committed progenitors.

Stem cells (in red) in the mesenchymal space around the gut branches (in green)

Publications

LIM-HD transcription factors control axial patterning and specify distinct neuronal and intestinal cell identities in planarians Molina, M.D.; Abduljabbar, D.; Guixeras, A.; Fraguas, S.; Cebrià, F. Open Biology 2023. Vol. 13. Pag. 230327. https://doi.org/10.1098/rsob.230327. https://royalsocietypublishing.org/doi/10.1098/rsob.230327.

Colorimetric whole-mount in situ hybridization in planarians Fraguas, S.; Molina, M.D.; Cebrià, F. In Gentile, L (eds). Schmidtea mediterranea. Methods in Molecular Biology 2023. Vol. 2680. Pag. 81-91. https://doi.orghttps://doi.org/10.1007/978-1-0716-3275-8_5/10.1007/978-1-0716-3275-8_5. https://pubmed.ncbi.nlm.nih.gov/37428372/.

FoxK1 is Required for Ectodermal Cell Differentiation During Planarian Regeneration Coronel-Córdoba, P.; Molina, M.D.; Cardona, G.; Fraguas, S.; Pascual-Carreras, E.; Saló, E.; Cebrià, F.; Adell, T. Frontiers in Cell & Developmental Biology 2022. Vol. 10:808045. doi: 10.3389/fcell.2022.808045. https://www.frontiersin.org/articles/10.3389/fcell.2022.808045/full?utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Cell_and_Developmental_Biology&id=808045.

Decoding Stem Cells: An Overview on Planarian Stem Cell Heterogeneity and Lineage Progression Molina, M.D.; Cebrià, F. Biomolecules 2021. Vol. 11. Pag. 1532. https://www.mdpi.com/2218-273X/11/10/1532.

CREB-binding protein (CBP) gene family regulates planarian survival and stem cell differentiation Fraguas, S.; Cárcel, S.; Vivancos, C.; Molina, M.D.; Ginés, J.; Mazariegos, J.; Sekaran, T.; Bartscherer, K.; Romero, R.; Cebrià, F. Developmental Biology 2021. Vol. 476. Pag. 53-67. 10.1016/j.ydbio.2021.02.008. https://pubmed.ncbi.nlm.nih.gov/33774010/.

Reactive oxygen species rescue regeneration after silencing the MAPK-ERK signaling pathway in Schmidtea mediterranea Jaenen, V.; Fraguas, S.; Bijnens, K.; Heleven, M.; Artois, T.; Romero, R.; Smeets, K.; Cebrià, F. Scientific Reports 2021. Vol. 11. Pag. 881. doi: 10.1038/s41598-020-79588-1. https://pubmed.ncbi.nlm.nih.gov/33441641/.

Planarians are here to stay and to teach us a lot on regeneration Cebrià, F. Seminars in Cell & Developmental Biology 2019. Vol. 87. Pag. 1-2. 10.1016/j.semcdb.2018.08.001. https://www.ncbi.nlm.nih.gov/pubmed/30081097.

The role of the EGFR signaling pathway in stem cell differentiation during planarian regeneration and homeostasis Barberán, S.; Cebrià, F. Seminars in Cell & Developmental Biology 2019. Vol. 87. Pag. 45-57. 10.1016/j.semcdb.2018.05.011. https://www.ncbi.nlm.nih.gov/pubmed/29775660.

Smed-egfr-4 is required for planarian eye regeneration Emili, E.; Pallarès, M.; Romero, R.; Cebrià, F. The International Journal of Developmental Biology 2019. Vol. 63. Pag. 9-15. 10.1387/ijdb.180361fc. https://www.ncbi.nlm.nih.gov/pubmed/30919917.

Rebuilding a planarian: from early signaling to final shape Cebrià F, Adell T, Saló E International Journal of Developmental Biology 2018. Vol. 62. Pag. 537-550. doi: 10.1387/ijdb.180042es. https://www.ncbi.nlm.nih.gov/pubmed/29938765.

Immunohistochemistry on paraffin-embedded planarian tissue sections Adell, T.; Barberán, S.; Sureda-Gómez,M.; Almuedo-Castillo, M.; de Sousa, N.; Cebrià, F. Methods in Molecular Biology 2018. Vol. 1774. Pag. 367-378. 10.1007/978-1-4939-7802-1_11. https://www.ncbi.nlm.nih.gov/pubmed/29916164.

Analyzing pERK activation during planarian regeneration Fraguas, S.; Umesono, Y.; Agata, K.; Cebrià, F. Methods in Molecular Biology 2017. Vol. 1487. Pag. 303-315. 10.1007/978-1-4939-6424-6_23. https://www.ncbi.nlm.nih.gov/pubmed/27924577.

Planarian body-wall muscle: regeneration and function beyond a simple skeletal support Cebrià, F. Frontiers in Cell & Developmental Biology 2016. Vol. 4. Pag. 8. 10.3389/fcell.2016.00008. https://www.ncbi.nlm.nih.gov/pubmed/26904543.

Evolution of the EGFR pathway in Metazoa and its diversification in the planarian Schmidtea mediterranea Barberán, S.; Martín-Durán, J.M.; Cebrià, F. Scientific Reports 2016. Vol. 6. Pag. 28071. 10.1038/srep28071. https://www.ncbi.nlm.nih.gov/pubmed/27325311.

The EGFR signaling pathway controls gut progenitor differentiation during planarian regeneration and homeostasis Barberán, S.; Fraguas, S.; Cebrià, F. Development 2016. Vol. 143. Pag. 2089-2102. 10.1242/dev.131995. https://www.ncbi.nlm.nih.gov/pubmed/27122174.

Reactive oxygen species in planarian regeneration: an upstream necessity for correct patterning and brain formation Pirotte, N.; Stevens, A.S.; Fraguas, S.; Plusquin, M.; Van Roten, A.; Van Belleghem, F.; Paesen, R.; Ameloot, M.; Cebrià, F.; Artois, T.; Smeets, K. Oxidative medicine and cellular longevity 2015. Vol. 2015. Pag. 392476. 10.1155/2015/392476. https://www.ncbi.nlm.nih.gov/pubmed/26180588.

egr-4, a target of EGFR signaling, is required for the formation of the brain primordia and head regeneration in planarians Fraguas, S.; Barberán, S.; Iglesias, M.; Rodríguez-Esteban, G.; Cebrià, F. Development 2014. Vol. 141. Pag. 1835-1847. 10.1242/dev.101345. https://www.ncbi.nlm.nih.gov/pubmed/24700819.

Regeneration of neuronal cell types in Schmidtea mediterranea: an immunohistochemical and expression study Fraguas, S.; Barberán, S.; Ibarra, B.; Stöger, L.; Cebrià, F. The International Journal of Developmental Biology 2012. Vol. 56. Pag. 143-153. 10.1387/ijdb.113428sf. https://www.ncbi.nlm.nih.gov/pubmed/22451002.

The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration Gentile, L.; Cebrià, F.; Bartscherer, K. Disease Models & Mechanisms 2011. Vol. 4. Pag. 12-19. 10.1242/dmm.006692. https://www.ncbi.nlm.nih.gov/pubmed/21135057.

Organizing the DV axis during planarian regeneration Molina, M.D.; Saló, E.; Cebrià, F. Communicative & integrative biology 2011. Vol. 4. Pag. 498-500. 10.4161/cib.4.4.15753. https://www.ncbi.nlm.nih.gov/pubmed/21966583.