Double homebox (DUX) retrogenes regulate early embryonic transcription and stem cell potency

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Title Double homebox (DUX) retrogenes regulate early embryonic transcription and stem cell potency
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Hendrickson, Peter
Date 2017-08
Description Following fertilization, mammalian embryos undergo a series of cleavage divisions during which embryonic cells are reprogrammed from a differentiated germ cell state to an undifferentiated embryonic state. Blastomeres of the 2-cell, 4-cell, and 8-cell (cleavage) embryo are ‘totipotent’, meaning they maintain the capacity to develop into all cell lineages of a developing embryo. This unique developmental potential is progressively lost in humans and other placental mammals as cells become restricted to an embryonic (inner cell mass, ICM) or extraembryonic (trophectoderm) lineage. Unlike pluripotent stem cells which can be derived from the ICM and have been extensively characterized, little is known about the totipotent cells of the cleavage stage embryo. What factors coordinate this dramatic reprogramming event and confer this unique developmental potential? Here, using RNA-sequencing, I profiled human cleavage stage embryos and identified a transcriptional program that specifically coincides with totipotency acquisition and loss. Remarkably, this totipotency transcriptional program is directly activated by DUX4 which is transiently and specifically expressed in 4-cell stage human embryos. The protein coding capacity of DUX4 has been conserved for over 100 million years; however, its evolutionary function/purpose has remained a complete mystery until now. By extending this work into mouse, I reveal a conserved functional role for DUX4-family genes in facilitating the mammalian embryonic reprogramming process through which totipotency is established.
Type Text
Publisher University of Utah
Subject Genetics; Developmental biology
Subject MESH Epigenesis, Genetic; Genes, Homeobox; Embryonic Development; Gene Expression Regulation, Developmental; Transcription Factors; Totipotent Stem Cells; Embryo, Mammalian
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of Double Homebox (DUX) Retrogenes Regulate Early Embryonic Transcription and Stem Cell Potency
Rights Management Copyright © Peter Hendrickson 2017
Format application/pdf
Format Medium application/pdf
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6wd8535
Setname ir_etd
ID 1348669
Reference URL https://collections.lib.utah.edu/ark:/87278/s6wd8535
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