Mouse Androgenetic Embryonic Stem Cells Differentiated to Multiple Cell Lineages in Three Embryonic Germ Layers <i>In Vitro</i>

Abstract

Abstract. The embryos of some rodents and primates can precede early development without the process of fertilization; however, they cease to develop after implantation because of restricted expressions of imprinting genes. Asexually developed embryos are classified into parthenote/gynogenote and androgenote by their genomic origins. Embryonic stem cells (ESCs) derived from asexual origins have also been reported. To date, ESCs derived from parthenogenetic embryos (PgESCs) have been established in some species, including humans, and the possibility to be alternative sources for autologous cell transplantation in regenerative medicine has been proposed. However, some developmental characteristics, which might be important for therapeutic applications, such as multiple differentiation capacity and transplantability of the ESCs of androgenetic origin (AgESCs) are uncertain. Here, we induced differentiation of mouse AgESCs and observed derivation of neural cells, cardiomyocytes and hepatocytes in vitro. Following differentiated embryoid body (EB) transplantation in various mouse strains including the strain of origin, we found that the EBs could engraft in theoretically MHC-matched strains. Our results indicate that AgESCs possess at least two important characteristics, multiple differentiation properties in vitro and transplantability after differentiation, and suggest that they can also serve as a source of histocompatible tissues for transplantation.

Two paternal genomes are compatible with dopaminergic in vitro and in vivo differentiation

“…While PG ES cell chimeras can survive postnatally with substantial contribution of ES cells (Sturm et al, 1994), AG ES cell chimeras typically exhibit severe defects and high lethality during fetal and postnatal stages (Mann et al, 1990;Narasimha et al, 1997). However, similar to ES cells derived from biparental (N) embryos, uniparental ES cells generate ecto-, meso-, and endodermal cell lineages in cell cultures including neural progenitor/stem cells and engrafting hematopoietic stem cells Eckardt et al, 2008;Eckardt et al, 2007;Lengerke et al, 2007;Teramura et al, 2009). We consider the analysis of AG ES cells relevant for two reasons: 1.)…”

Progenitor Cells for Regenerative Medicine and Consequences of ART and Cloning-Associated Epimutations

“…In human gynogenetic pESCs, lack of expression from paternally expressed loci reveals their uniparental origin [47,48]. The argument has been made that some altered imprinting patterns may be tolerable for downstream regenerative medicine applications if the desired tissue does not express the loci in question [44,52]. The ability of mouse pESCs to reconstitute hematopoietic lineages, despite relaxed imprinting found in both gynogenetic and androgenetic-derived pESCs, supports this contention [53].…”

“…The ability of mouse pESCs to reconstitute hematopoietic lineages, despite relaxed imprinting found in both gynogenetic and androgenetic-derived pESCs, supports this contention [53]. However, there is common recognition of the need for further transplantation studies for comprehensive analysis of any safety issues which may be relevant to human regenerative medicine applications using pESCs [44,52].…”

“…Similarly, mouse androgenetic pESCs demonstrate similar traits of pluripotency [52]. The potential of pESCs for cell-based regenerative therapies is illustrated by the hematopoietic reconstitution of mice by both gynogenetic and androgenetic pESCs [53].…”

Analysis of proteomic profiling of mouse embryonic stem cells derived from fertilized, parthenogenetic and androgenetic blastocysts

“…Dinger et al [20] observed widespread contributions from aESCs in fetal chimeric mice and reported that their neural differentiation potential, in terms of self-renewal properties of neural stem cells, did not differ from that of normal biparental fESCs [20]. In addition, aESCs are able to differentiate into various cell types of all three embryonic germ layers [21]. Together, homozygous ESCs, or at least pESCs, are indistinguishable from fESCs with respect to tissue/organ contribution.…”