Asset Details
Do you wish to reserve the book?
Genome editing reveals a role for OCT4 in human embryogenesis
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Genome editing reveals a role for OCT4 in human embryogenesis
Do you wish to request the book?
Genome editing reveals a role for OCT4 in human embryogenesis
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Genome editing reveals a role for OCT4 in human embryogenesis
2017
Overview
Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use CRISPR–Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (
POU5F1
) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in
POU5F1-
null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as
CDX2
, but also for regulators of the pluripotent epiblast, including
NANOG
. By contrast,
Pou5f1
-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR–Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.
Genome editing in human zygotes shows that OCT4 is required for normal development at an earlier stage in humans than in mice.
Investigating gene function in embryogenesis
The molecular mechanisms that direct early cell fate decisions in human embryos are currently unclear. Kathy Niakan and colleagues have used CRISPR–Cas9-mediated genome editing to analyse the role of the pluripotency transcription factor OCT4 during human embryogenesis, and uncover some unexpected functions. They first defined the most efficient OCT4-targeting single-cell RNA and delivery method using a combination of analysis in human embryonic stem cells and mouse embryos, before moving to donated diploid human zygotes. They find that OCT4 is required early in development to regulate the expression of genes in extra-embryonic trophectoderm, which makes up the placenta, and of pluripotent genes such as
NANOG
, which define the pluripotent epiblast.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/31
/ 14
/ 14/1
/ 14/19
/ 38
/ 38/23
/ 38/77
/ 38/88
/ 38/91
/ 45/41
/ 45/90
/ 64
/ 64/60
/ Animals
/ CRISPR
/ CRISPR-Cas Systems - genetics
/ DNA
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - embryology
/ Embryo, Mammalian - metabolism
/ Embryonic Development - genetics
/ Embryos
/ Female
/ Gene Expression Regulation, Developmental
/ Genes
/ Genomes
/ Human Embryonic Stem Cells - cytology
/ Human Embryonic Stem Cells - metabolism
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Male
/ Methods
/ Mice
/ Mutation
/ Nanog Homeobox Protein - genetics
/ Nanog Homeobox Protein - metabolism
/ Octamer Transcription Factor-3 - deficiency
/ Octamer Transcription Factor-3 - genetics
/ Octamer Transcription Factor-3 - metabolism
/ Proteins
/ RNA
/ Science
/ Zygotes
