β-catenin perturbations control differentiation programs in mouse embryonic stem cells
Abstract The Wnt/β-catenin pathway is involved in development, cancer and embryonic stem cell (ESC) maintenance; its dual role in stem cell self-renewal and differentiation is still controversial. Here, by applying anin vitrosystem enabling inducible gene expression control, we report that moderate induction of transcriptionally active exogenous β- catenin in β-catenin null mouse ESCs promotes epiblast-like cell (EpiLC) derivationin vitro. Instead, in wild type cells moderate chemical pre-activation of the Wnt/β-catenin pathway promotes EpiLCin vitroderivation. Finally, we suggest that moderate β- catenin levels in β-catenin null mouse ESCs favour early stem cell commitment towards mesoderm if the exogenous protein is induced only in the ‘ground state’ of pluripotency condition, or endoderm if the induction is maintained during the differentiation. Overall, our results confirm previous findings about the role of β-catenin in pluripotency and differentiation, while indicating a role for its doses in promoting specific differentiation programs..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 01. Okt. Zur Gesamtaufnahme - year:2023 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Pedone, Elisa [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| doi: |
10.1101/2020.05.15.098137 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI017918197 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI017918197 | ||
| 003 | DE-627 | ||
| 005 | 20231205150511.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200518s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.05.15.098137 |2 doi | |
| 035 | |a (DE-627)XBI017918197 | ||
| 035 | |a (biorXiv)10.1101/2020.05.15.098137 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Pedone, Elisa |e verfasserin |0 (orcid)0000-0001-9467-8207 |4 aut | |
| 245 | 1 | 0 | |a β-catenin perturbations control differentiation programs in mouse embryonic stem cells |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract The Wnt/β-catenin pathway is involved in development, cancer and embryonic stem cell (ESC) maintenance; its dual role in stem cell self-renewal and differentiation is still controversial. Here, by applying anin vitrosystem enabling inducible gene expression control, we report that moderate induction of transcriptionally active exogenous β- catenin in β-catenin null mouse ESCs promotes epiblast-like cell (EpiLC) derivationin vitro. Instead, in wild type cells moderate chemical pre-activation of the Wnt/β-catenin pathway promotes EpiLCin vitroderivation. Finally, we suggest that moderate β- catenin levels in β-catenin null mouse ESCs favour early stem cell commitment towards mesoderm if the exogenous protein is induced only in the ‘ground state’ of pluripotency condition, or endoderm if the induction is maintained during the differentiation. Overall, our results confirm previous findings about the role of β-catenin in pluripotency and differentiation, while indicating a role for its doses in promoting specific differentiation programs. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Failli, Mario |0 (orcid)0000-0002-3490-7714 |4 aut | |
| 700 | 1 | |a Gambardella, Gennaro |0 (orcid)0000-0001-7517-1347 |4 aut | |
| 700 | 1 | |a De Cegli, Rossella |4 aut | |
| 700 | 1 | |a La Regina, Antonella |0 (orcid)0000-0001-9683-180X |4 aut | |
| 700 | 1 | |a di Bernardo, Diego |0 (orcid)0000-0002-1911-7407 |4 aut | |
| 700 | 1 | |a Marucci, Lucia |0 (orcid)0000-0002-7553-6358 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2023) vom: 01. Okt. |
| 773 | 1 | 8 | |g year:2023 |g day:01 |g month:10 |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.isci.2022.103756 |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.05.15.098137 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 951 | |a AR | ||
| 952 | |j 2023 |b 01 |c 10 | ||