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000305779 0247_ $$2doi$$a10.1016/j.stem.2019.03.018
000305779 0247_ $$2pmid$$apmid:31031139
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000305779 0247_ $$2ISSN$$a1875-9777
000305779 037__ $$aDKFZ-2025-02396
000305779 041__ $$aEnglish
000305779 082__ $$a570
000305779 1001_ $$aBenchetrit, Hana$$b0
000305779 245__ $$aDirect Induction of the Three Pre-implantation Blastocyst Cell Types from Fibroblasts.
000305779 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2019
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000305779 520__ $$aFollowing fertilization, totipotent cells undergo asymmetric cell divisions, resulting in three distinct cell types in the late pre-implantation blastocyst: epiblast (Epi), primitive endoderm (PrE), and trophectoderm (TE). Here, we aim to understand whether these three cell types can be induced from fibroblasts by one combination of transcription factors. By utilizing a sophisticated fluorescent knockin reporter system, we identified a combination of five transcription factors, Gata3, Eomes, Tfap2c, Myc, and Esrrb, that can reprogram fibroblasts into induced pluripotent stem cells (iPSCs), induced trophoblast stem cells (iTSCs), and induced extraembryonic endoderm stem cells (iXENs), concomitantly. In-depth transcriptomic, chromatin, and epigenetic analyses provide insights into the molecular mechanisms that underlie the reprogramming process toward the three cell types. Mechanistically, we show that the interplay between Esrrb and Eomes during the reprogramming process determines cell fate, where high levels of Esrrb induce a XEN-like state that drives pluripotency and high levels of Eomes drive trophectodermal fate.
000305779 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000305779 650_7 $$2Other$$aEomes
000305779 650_7 $$2Other$$aEsrrb
000305779 650_7 $$2Other$$aearly embryonic development
000305779 650_7 $$2Other$$ainduced extraembryonic endoderm stem cells
000305779 650_7 $$2Other$$ainduced pluripotent stem cells
000305779 650_7 $$2Other$$ainduced trophoblast stem cells
000305779 650_7 $$2Other$$ainner cell mass
000305779 650_7 $$2Other$$aprimitive endoderm
000305779 650_7 $$2Other$$areprogramming
000305779 650_7 $$2Other$$atrophectoderm
000305779 650_7 $$2NLM Chemicals$$aEOMES protein, human
000305779 650_7 $$2NLM Chemicals$$aESRRB protein, human
000305779 650_7 $$2NLM Chemicals$$aReceptors, Estrogen
000305779 650_7 $$2NLM Chemicals$$aT-Box Domain Proteins
000305779 650_7 $$2NLM Chemicals$$aTranscription Factors
000305779 650_2 $$2MeSH$$aAnimals
000305779 650_2 $$2MeSH$$aBlastocyst: physiology
000305779 650_2 $$2MeSH$$aCell Differentiation
000305779 650_2 $$2MeSH$$aCell Lineage
000305779 650_2 $$2MeSH$$aCells, Cultured
000305779 650_2 $$2MeSH$$aCellular Reprogramming
000305779 650_2 $$2MeSH$$aEmbryo Implantation
000305779 650_2 $$2MeSH$$aEndoderm: physiology
000305779 650_2 $$2MeSH$$aFibroblasts: physiology
000305779 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: physiology
000305779 650_2 $$2MeSH$$aMice
000305779 650_2 $$2MeSH$$aReceptors, Estrogen: genetics
000305779 650_2 $$2MeSH$$aReceptors, Estrogen: metabolism
000305779 650_2 $$2MeSH$$aT-Box Domain Proteins: genetics
000305779 650_2 $$2MeSH$$aT-Box Domain Proteins: metabolism
000305779 650_2 $$2MeSH$$aTranscription Factors: metabolism
000305779 650_2 $$2MeSH$$aTrophoblasts: physiology
000305779 7001_ $$aJaber, Mohammad$$b1
000305779 7001_ $$aZayat, Valery$$b2
000305779 7001_ $$aSebban, Shulamit$$b3
000305779 7001_ $$aPushett, Avital$$b4
000305779 7001_ $$aMakedonski, Kirill$$b5
000305779 7001_ $$aZakheim, Zvi$$b6
000305779 7001_ $$aRadwan, Ahmed$$b7
000305779 7001_ $$aMaoz, Noam$$b8
000305779 7001_ $$aLasry, Rachel$$b9
000305779 7001_ $$aRenous, Noa$$b10
000305779 7001_ $$aInbar, Michal$$b11
000305779 7001_ $$aRam, Oren$$b12
000305779 7001_ $$aKaplan, Tommy$$b13
000305779 7001_ $$aBuganim, Yosef$$b14
000305779 773__ $$0PERI:(DE-600)2375356-0$$a10.1016/j.stem.2019.03.018$$gVol. 24, no. 6, p. 983 - 994.e7$$n6$$p983 - 994.e7$$tCell stem cell$$v24$$x1934-5909$$y2019
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