Differentiation is accompanied by a progressive loss in transcriptional memory
Abstract Background Cell differentiation requires the integration of two opposite processes, a stabilizing cellular memory, especially at the transcriptional scale, and a burst of gene expression variability which follows the differentiation induction. Therefore, the actual capacity of a cell to und...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-03-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-024-01846-9 |
| _version_ | 1827315738401046528 |
|---|---|
| author | Camille Fourneaux Laëtitia Racine Catherine Koering Sébastien Dussurgey Elodie Vallin Alice Moussy Romuald Parmentier Fanny Brunard Daniel Stockholm Laurent Modolo Franck Picard Olivier Gandrillon Andras Paldi Sandrine Gonin-Giraud |
| author_facet | Camille Fourneaux Laëtitia Racine Catherine Koering Sébastien Dussurgey Elodie Vallin Alice Moussy Romuald Parmentier Fanny Brunard Daniel Stockholm Laurent Modolo Franck Picard Olivier Gandrillon Andras Paldi Sandrine Gonin-Giraud |
| author_sort | Camille Fourneaux |
| collection | DOAJ |
| description | Abstract Background Cell differentiation requires the integration of two opposite processes, a stabilizing cellular memory, especially at the transcriptional scale, and a burst of gene expression variability which follows the differentiation induction. Therefore, the actual capacity of a cell to undergo phenotypic change during a differentiation process relies upon a modification in this balance which favors change-inducing gene expression variability. However, there are no experimental data providing insight on how fast the transcriptomes of identical cells would diverge on the scale of the very first two cell divisions during the differentiation process. Results In order to quantitatively address this question, we developed different experimental methods to recover the transcriptomes of related cells, after one and two divisions, while preserving the information about their lineage at the scale of a single cell division. We analyzed the transcriptomes of related cells from two differentiation biological systems (human CD34+ cells and T2EC chicken primary erythrocytic progenitors) using two different single-cell transcriptomics technologies (scRT-qPCR and scRNA-seq). Conclusions We identified that the gene transcription profiles of differentiating sister cells are more similar to each other than to those of non-related cells of the same type, sharing the same environment and undergoing similar biological processes. More importantly, we observed greater discrepancies between differentiating sister cells than between self-renewing sister cells. Furthermore, a progressive increase in this divergence from first generation to second generation was observed when comparing differentiating cousin cells to self renewing cousin cells. Our results are in favor of a gradual erasure of transcriptional memory during the differentiation process. |
| first_indexed | 2024-04-24T23:02:21Z |
| format | Article |
| id | doaj.art-29a9a65391ea4083ac4d52516b373d50 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-24T23:02:21Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-29a9a65391ea4083ac4d52516b373d502024-03-17T12:38:22ZengBMCBMC Biology1741-70072024-03-0122112010.1186/s12915-024-01846-9Differentiation is accompanied by a progressive loss in transcriptional memoryCamille Fourneaux0Laëtitia Racine1Catherine Koering2Sébastien Dussurgey3Elodie Vallin4Alice Moussy5Romuald Parmentier6Fanny Brunard7Daniel Stockholm8Laurent Modolo9Franck Picard10Olivier Gandrillon11Andras Paldi12Sandrine Gonin-Giraud13Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Ecole Pratique des Hautes Etudes, PSL Research University, Sorbonne Université, INSERM, CRSALaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Plateforme AniRA-Cytométrie, Université Claude Bernard Lyon 1, CNRS UAR3444, Inserm US8, ENS de Lyon, SFR BiosciencesLaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Ecole Pratique des Hautes Etudes, PSL Research University, Sorbonne Université, INSERM, CRSAEcole Pratique des Hautes Etudes, PSL Research University, Sorbonne Université, INSERM, CRSALaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Ecole Pratique des Hautes Etudes, PSL Research University, Sorbonne Université, INSERM, CRSALaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Ecole Pratique des Hautes Etudes, PSL Research University, Sorbonne Université, INSERM, CRSALaboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, CNRS, UMR5239, Université Claude Bernard Lyon 1Abstract Background Cell differentiation requires the integration of two opposite processes, a stabilizing cellular memory, especially at the transcriptional scale, and a burst of gene expression variability which follows the differentiation induction. Therefore, the actual capacity of a cell to undergo phenotypic change during a differentiation process relies upon a modification in this balance which favors change-inducing gene expression variability. However, there are no experimental data providing insight on how fast the transcriptomes of identical cells would diverge on the scale of the very first two cell divisions during the differentiation process. Results In order to quantitatively address this question, we developed different experimental methods to recover the transcriptomes of related cells, after one and two divisions, while preserving the information about their lineage at the scale of a single cell division. We analyzed the transcriptomes of related cells from two differentiation biological systems (human CD34+ cells and T2EC chicken primary erythrocytic progenitors) using two different single-cell transcriptomics technologies (scRT-qPCR and scRNA-seq). Conclusions We identified that the gene transcription profiles of differentiating sister cells are more similar to each other than to those of non-related cells of the same type, sharing the same environment and undergoing similar biological processes. More importantly, we observed greater discrepancies between differentiating sister cells than between self-renewing sister cells. Furthermore, a progressive increase in this divergence from first generation to second generation was observed when comparing differentiating cousin cells to self renewing cousin cells. Our results are in favor of a gradual erasure of transcriptional memory during the differentiation process.https://doi.org/10.1186/s12915-024-01846-9Cell differentiationGene expression variabilityTranscriptomeSister cellsTranscriptional memory |
| spellingShingle | Camille Fourneaux Laëtitia Racine Catherine Koering Sébastien Dussurgey Elodie Vallin Alice Moussy Romuald Parmentier Fanny Brunard Daniel Stockholm Laurent Modolo Franck Picard Olivier Gandrillon Andras Paldi Sandrine Gonin-Giraud Differentiation is accompanied by a progressive loss in transcriptional memory BMC Biology Cell differentiation Gene expression variability Transcriptome Sister cells Transcriptional memory |
| title | Differentiation is accompanied by a progressive loss in transcriptional memory |
| title_full | Differentiation is accompanied by a progressive loss in transcriptional memory |
| title_fullStr | Differentiation is accompanied by a progressive loss in transcriptional memory |
| title_full_unstemmed | Differentiation is accompanied by a progressive loss in transcriptional memory |
| title_short | Differentiation is accompanied by a progressive loss in transcriptional memory |
| title_sort | differentiation is accompanied by a progressive loss in transcriptional memory |
| topic | Cell differentiation Gene expression variability Transcriptome Sister cells Transcriptional memory |
| url | https://doi.org/10.1186/s12915-024-01846-9 |
| work_keys_str_mv | AT camillefourneaux differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT laetitiaracine differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT catherinekoering differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT sebastiendussurgey differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT elodievallin differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT alicemoussy differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT romualdparmentier differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT fannybrunard differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT danielstockholm differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT laurentmodolo differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT franckpicard differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT oliviergandrillon differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT andraspaldi differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory AT sandrinegoningiraud differentiationisaccompaniedbyaprogressivelossintranscriptionalmemory |