title: Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm.
abstract: 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.
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Waghray
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10029, USA.
authors.forename: Néstor
authors.initials: N
authors.lastname: Saiz
authors.affiliation: Graduate School, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Anitha D
authors.initials: AD
authors.lastname: Jayaprakash
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; I3S - Instituto de Investigação e Inovação em Saúde & INEB - Instituto de Engenharia Biomédica, Universidade do Porto, 4150-180 Porto, Portugal; Faculdade de Engenharia da Universidade do Porto, 4200-465 Porto, Portugal.
authors.forename: Ana G
authors.initials: AG
authors.lastname: Freire
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Papatsenko
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Carlos-Filipe
authors.initials: CF
authors.lastname: Pereira
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Dung-Fang
authors.initials: DF
authors.lastname: Lee
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Brosh
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Chang
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Henia
authors.initials: H
authors.lastname: Darr
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Gingold
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kelley
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pharmacology and System Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schaniel
authors.affiliation: Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10029, USA.
authors.forename: Anna-Katerina
authors.initials: AK
authors.lastname: Hadjantonakis
authors.affiliation: Developmental and Regenerative Biology, The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Pharmacology and System Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: ihor.lemischka@mssm.edu.
authors.forename: Ihor R
authors.initials: IR
authors.lastname: Lemischka
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C462180:Dppa3 protein, mouse; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse