TY - JOUR
T1 - Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm
AU - Waghray, Avinash
AU - Saiz, Néstor
AU - Jayaprakash, Anitha D.
AU - Freire, Ana G.
AU - Papatsenko, Dmitri
AU - Pereira, Carlos Filipe
AU - Lee, Dung Fang
AU - Brosh, Ran
AU - Chang, Betty
AU - Darr, Henia
AU - Gingold, Julian
AU - Kelley, Kevin
AU - Schaniel, Christoph
AU - Hadjantonakis, Anna Katerina
AU - Lemischka, Ihor R.
PY - 2015/7/14
Y1 - 2015/7/14
N2 - Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also, Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps to maintain a naive pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state toward mesoderm differentiation.
AB - Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also, Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps to maintain a naive pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state toward mesoderm differentiation.
UR - https://www.scopus.com/pages/publications/84937523983
U2 - 10.1016/j.stemcr.2015.05.009
DO - 10.1016/j.stemcr.2015.05.009
M3 - Article
C2 - 26095607
AN - SCOPUS:84937523983
SN - 2213-6711
VL - 5
SP - 97
EP - 110
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -
