Distinct Imprinting Signatures and Biased Differentiation of Human Androgenetic and Parthenogenetic Embryonic Stem Cells

Abstract

Highlights d Generation of human androgenetic and parthenogenetic ESCs (aESCs and pESCs) d Comparing aESCs and pESCs identifies known and formerly undescribed imprinted genes d The uniparental cells show tissue-specific parent-of-origin differentiation biases d The imprinted gene IGF2 is involved in hepatic differentiation bias of human aESCs

Dysregulated gene expression of imprinted and X-linked genes: a link to poor development of bovine haploid androgenetic embryos

“…In addition, androgenetic embryos that progressed beyond ZGA underwent a second arrest at the morula stage. Similar results have been reported in cattle (Winger et al, 1997; Vichera et al, 2011), sheep (Matsukawa et al, 2007), mouse (Kono et al, 1993; Latham et al, 2002; Hu et al, 2015a; Hu et al, 2015b), and human species (Kuznyetsov et al, 2007; Sagi et al, 2019). Further development to the blastocyst stage, of both haploid parthenotes and androgenotes was severely limited compared to diploid embryos, evidencing a deleterious effect of haploidy on the very early stage of embryogenesis.…”

“…In agreement with these findings others have indicated that enucleation during the telophase stage of second meiosis (TII) shows advantages over enucleation at the metaphase II stage. For instance, TII enucleation allows the removal of smaller ooplasm fragments (Bordignon and Smith, 1998; Lee and Campbell, 2006), can be performed in the absence of UV irradiation (Kuznyetsov et al, 2007; Sagi et al, 2019), and it also allows the selection of the best oocytes for enucleation through the exclusive use oocytes that respond promptly to fertilization by second polar body extrusion (Kuznyetsov et al, 2007).…”

“…However, in bovine species the efforts to visualize and enucleate zygotes at pronuclear stages is hampered by the presence of dense lipid vesicles, and thus, usually, removal of the oocytes metaphase spindle is performed pre-IVF, as in the case of SCNT, at approximately 18 to 20 h after beginning of in vitro maturation (MII enucleation). Otherwise, during the telophase to anaphase transition of meiosis II the second polar body is a reliable indicator of the position of the oocyte’s spindle and it can be reliably used to enucleate mammalian oocytes (Bordignon and Smith, 1998; Kuznyetsov et al, 2007; Sagi et al, 2019).…”

Precise allele-specific genome editing by spatiotemporal control of CRISPR-Cas9 via pronuclear transplantation

“…As mentioned above, monoallelic knockout animal models carrying heritable lethal mutations could be generated efficiently in the F0 generation, while this is not achievable by traditional methods 18 . As several recent studies have revealed, abundant parental-specific gene expression exerts a great influence on pre-or post-implantation development, but diseases resulting from these early changes are difficult to ascertain due to the unobservable symptom in early stages of pregnancy 24,50,51 . However, Past-CRISPR has great advantages in terms of the functional verification of individual parent-of-origin genes, including imprinted gene candidates.…”

From Mother or Father: Uniparental Embryos Uncover Parent-of-Origin Effects in Humans

“…In mammals, both parents make unique contributions to the offspring and maternal and paternal genomes are required for development. Two recent papers in Cell Stem Cell (Leng et al, 2019;Sagi et al, 2019) study uniparental embryos and uniparental embryonic stem cells to interrogate parent-of-origin effects in human embryogenesis.…”