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Transcription factor-based transdifferentiation of human embryonic to trophoblast stem cells
Faculty
Science
Year:
2024
Type of Publication:
ZU Hosted
Pages:
26
Authors:
Ahmed Mohamed Abdelbaky Abedulaal
Staff Zu Site
Abstract In Staff Site
Journal:
Development The Company of Biologists
Volume:
Keywords :
Transcription factor-based transdifferentiation , human embryonic , trophoblast
Abstract:
During the first week of development, human embryos form a blastocyst composed of an inner cell mass and trophectoderm (TE) cells, the latter of which are progenitors of placental trophoblast. Here, we investigated the expression of transcripts in the human TE from early to late blastocyst stages. We identified enrichment of the transcription factors GATA2, GATA3, TFAP2C and KLF5 and characterised their protein expression dynamics across TE development. By inducible overexpression and mRNA transfection, we determined that these factors, together with MYC, are sufficient to establish induced trophoblast stem cells (iTSCs) from primed human embryonic stem cells. These iTSCs self-renew and recapitulate morphological characteristics, gene expression profiles, and directed differentiation potential, similar to existing human TSCs. Systematic omission of each, or combinations of factors, revealed the crucial importance of GATA2 and GATA3 for iTSC transdifferentiation. Altogether, these findings provide insights into the transcription factor network that may be operational in the human TE and broaden the methods for establishing cellular models of early human placental progenitor cells, which may be useful in the future to model placental-associated diseases.
Author Related Publications
Ahmed Mohamed Abdelbaky Abedulaal, "Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus", Royal Society_Open Biology 8(6):170272Royal Society, 2018
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Ahmed Mohamed Abdelbaky Abedulaal, "AURKA destruction is decoupled from its activity at mitotic exit but essential to suppress interphase activity", The Company of Biologists, 2020
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Ahmed Mohamed Abdelbaky Abedulaal, "Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool", Nature, 2021
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Ahmed Mohamed Abdelbaky Abedulaal, "Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool", Nature, 2021
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Ahmed Mohamed Abdelbaky Abedulaal, "Revisiting degron motifs in human AURKA required for its targeting by APC/C-FZR1", EMBO Press, Rockefeller University Press and Cold Spring Harbor Laboratory Press, 2022
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Department Related Publications
Iman Hassan Mohammed Sheikh, "Scanning Electron Microscopic Studies of Gill Arches and Rakers in Relation to Feeding Habits of Some Fresh Water Fishes", Elsevier, 2013
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Iman Hassan Mohammed Sheikh, "Light and scanning electron microscopical studies of the tongue in the hooded crow (Aves: Corvus corone cornix)", Elsevier, 2014
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Iman Hassan Mohammed Sheikh, "Ultramorphological and histological studies on the tongue of the common kingfisher in relation to its feeding", Elsevier, 2014
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