Evidence for close molecular proximity between reverting and undifferentiated cells
Abstract Background According to Waddington’s epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or “attractor states” to reach its stable diffe...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-022-01363-7 |
| _version_ | 1828760195601268736 |
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| author | Souad Zreika Camille Fourneaux Elodie Vallin Laurent Modolo Rémi Seraphin Alice Moussy Elias Ventre Matteo Bouvier Anthony Ozier-Lafontaine Arnaud Bonnaffoux Franck Picard Olivier Gandrillon Sandrine Gonin-Giraud |
| author_facet | Souad Zreika Camille Fourneaux Elodie Vallin Laurent Modolo Rémi Seraphin Alice Moussy Elias Ventre Matteo Bouvier Anthony Ozier-Lafontaine Arnaud Bonnaffoux Franck Picard Olivier Gandrillon Sandrine Gonin-Giraud |
| author_sort | Souad Zreika |
| collection | DOAJ |
| description | Abstract Background According to Waddington’s epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or “attractor states” to reach its stable differentiated state. However, it is now clear that some committed cells can retain a certain degree of plasticity and reacquire phenotypical characteristics of a more pluripotent cell state. In line with this dynamic model, we have previously shown that differentiating cells (chicken erythrocytic progenitors (T2EC)) retain for 24 h the ability to self-renew when transferred back in self-renewal conditions. Despite those intriguing and promising results, the underlying molecular state of those “reverting” cells remains unexplored. The aim of the present study was therefore to molecularly characterize the T2EC reversion process by combining advanced statistical tools to make the most of single-cell transcriptomic data. For this purpose, T2EC, initially maintained in a self-renewal medium (0H), were induced to differentiate for 24H (24H differentiating cells); then, a part of these cells was transferred back to the self-renewal medium (48H reverting cells) and the other part was maintained in the differentiation medium for another 24H (48H differentiating cells). For each time point, cell transcriptomes were generated using scRT-qPCR and scRNAseq. Results Our results showed a strong overlap between 0H and 48H reverting cells when applying dimensional reduction. Moreover, the statistical comparison of cell distributions and differential expression analysis indicated no significant differences between these two cell groups. Interestingly, gene pattern distributions highlighted that, while 48H reverting cells have gene expression pattern more similar to 0H cells, they are not completely identical, which suggest that for some genes a longer delay may be required for the cells to fully recover. Finally, sparse PLS (sparse partial least square) analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells. Conclusions Altogether, we show that reverting cells return to an earlier molecular state almost identical to undifferentiated cells and demonstrate a previously undocumented physiological and molecular plasticity during the differentiation process, which most likely results from the dynamic behavior of the underlying molecular network. |
| first_indexed | 2024-12-11T01:10:12Z |
| format | Article |
| id | doaj.art-c2d10c001e0f4d87920f7ade838d64ab |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-11T01:10:12Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-c2d10c001e0f4d87920f7ade838d64ab2022-12-22T01:26:05ZengBMCBMC Biology1741-70072022-07-0120111610.1186/s12915-022-01363-7Evidence for close molecular proximity between reverting and undifferentiated cellsSouad Zreika0Camille Fourneaux1Elodie Vallin2Laurent Modolo3Rémi Seraphin4Alice Moussy5Elias Ventre6Matteo Bouvier7Anthony Ozier-Lafontaine8Arnaud Bonnaffoux9Franck Picard10Olivier Gandrillon11Sandrine Gonin-Giraud12Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Ecole Pratique des Hautes Etudes, PSL Research University, UMRS951, INSERM, Univ-EvryLaboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Nantes Université, Centrale Nantes, Laboratoire de mathématiques Jean Leray, LMJLLaboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratory of Biology and Modelling of the Cell, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Abstract Background According to Waddington’s epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or “attractor states” to reach its stable differentiated state. However, it is now clear that some committed cells can retain a certain degree of plasticity and reacquire phenotypical characteristics of a more pluripotent cell state. In line with this dynamic model, we have previously shown that differentiating cells (chicken erythrocytic progenitors (T2EC)) retain for 24 h the ability to self-renew when transferred back in self-renewal conditions. Despite those intriguing and promising results, the underlying molecular state of those “reverting” cells remains unexplored. The aim of the present study was therefore to molecularly characterize the T2EC reversion process by combining advanced statistical tools to make the most of single-cell transcriptomic data. For this purpose, T2EC, initially maintained in a self-renewal medium (0H), were induced to differentiate for 24H (24H differentiating cells); then, a part of these cells was transferred back to the self-renewal medium (48H reverting cells) and the other part was maintained in the differentiation medium for another 24H (48H differentiating cells). For each time point, cell transcriptomes were generated using scRT-qPCR and scRNAseq. Results Our results showed a strong overlap between 0H and 48H reverting cells when applying dimensional reduction. Moreover, the statistical comparison of cell distributions and differential expression analysis indicated no significant differences between these two cell groups. Interestingly, gene pattern distributions highlighted that, while 48H reverting cells have gene expression pattern more similar to 0H cells, they are not completely identical, which suggest that for some genes a longer delay may be required for the cells to fully recover. Finally, sparse PLS (sparse partial least square) analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells. Conclusions Altogether, we show that reverting cells return to an earlier molecular state almost identical to undifferentiated cells and demonstrate a previously undocumented physiological and molecular plasticity during the differentiation process, which most likely results from the dynamic behavior of the underlying molecular network.https://doi.org/10.1186/s12915-022-01363-7Cell-fate reversionCell differentiationErythroid progenitorsSingle-cell RNA-seqSingle-cell RT-qPCR |
| spellingShingle | Souad Zreika Camille Fourneaux Elodie Vallin Laurent Modolo Rémi Seraphin Alice Moussy Elias Ventre Matteo Bouvier Anthony Ozier-Lafontaine Arnaud Bonnaffoux Franck Picard Olivier Gandrillon Sandrine Gonin-Giraud Evidence for close molecular proximity between reverting and undifferentiated cells BMC Biology Cell-fate reversion Cell differentiation Erythroid progenitors Single-cell RNA-seq Single-cell RT-qPCR |
| title | Evidence for close molecular proximity between reverting and undifferentiated cells |
| title_full | Evidence for close molecular proximity between reverting and undifferentiated cells |
| title_fullStr | Evidence for close molecular proximity between reverting and undifferentiated cells |
| title_full_unstemmed | Evidence for close molecular proximity between reverting and undifferentiated cells |
| title_short | Evidence for close molecular proximity between reverting and undifferentiated cells |
| title_sort | evidence for close molecular proximity between reverting and undifferentiated cells |
| topic | Cell-fate reversion Cell differentiation Erythroid progenitors Single-cell RNA-seq Single-cell RT-qPCR |
| url | https://doi.org/10.1186/s12915-022-01363-7 |
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