TY  - JOUR
AU  - Benchetrit, Hana
AU  - Jaber, Mohammad
AU  - Zayat, Valery
AU  - Sebban, Shulamit
AU  - Pushett, Avital
AU  - Makedonski, Kirill
AU  - Zakheim, Zvi
AU  - Radwan, Ahmed
AU  - Maoz, Noam
AU  - Lasry, Rachel
AU  - Renous, Noa
AU  - Inbar, Michal
AU  - Ram, Oren
AU  - Kaplan, Tommy
AU  - Buganim, Yosef
TI  - Direct Induction of the Three Pre-implantation Blastocyst Cell Types from Fibroblasts.
JO  - Cell stem cell
VL  - 24
IS  - 6
SN  - 1934-5909
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DKFZ-2025-02396
SP  - 983 - 994.e7
PY  - 2019
N1  - #DKFZ-MOST-Ca177#
AB  - Following 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.
KW  - Animals
KW  - Blastocyst: physiology
KW  - Cell Differentiation
KW  - Cell Lineage
KW  - Cells, Cultured
KW  - Cellular Reprogramming
KW  - Embryo Implantation
KW  - Endoderm: physiology
KW  - Fibroblasts: physiology
KW  - Induced Pluripotent Stem Cells: physiology
KW  - Mice
KW  - Receptors, Estrogen: genetics
KW  - Receptors, Estrogen: metabolism
KW  - T-Box Domain Proteins: genetics
KW  - T-Box Domain Proteins: metabolism
KW  - Transcription Factors: metabolism
KW  - Trophoblasts: physiology
KW  - Eomes (Other)
KW  - Esrrb (Other)
KW  - early embryonic development (Other)
KW  - induced extraembryonic endoderm stem cells (Other)
KW  - induced pluripotent stem cells (Other)
KW  - induced trophoblast stem cells (Other)
KW  - inner cell mass (Other)
KW  - primitive endoderm (Other)
KW  - reprogramming (Other)
KW  - trophectoderm (Other)
KW  - EOMES protein, human (NLM Chemicals)
KW  - ESRRB protein, human (NLM Chemicals)
KW  - Receptors, Estrogen (NLM Chemicals)
KW  - T-Box Domain Proteins (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31031139
C2  - pmc:PMC6561721
DO  - DOI:10.1016/j.stem.2019.03.018
UR  - https://inrepo02.dkfz.de/record/305779
ER  -