Generation of Induced Pluripotent Stem Cells from the Prairie Vole

Abstract

The vast majority of animals mate more or less promiscuously. A few mammals, including humans, utilize more restrained mating strategies that entail a longer term affiliation with a single mating partner. Such pair bonding mating strategies have been resistant to genetic analysis because of a lack of suitable model organisms. Prairie voles are small mouse-like rodents that form enduring pair bonds in the wild as well as in the laboratory, and consequently they have been used widely to study social bonding behavior. The lack of targeted genetic approaches in this species however has restricted the study of the molecular and neural circuit basis of pair bonds. As a first step in rendering the prairie vole amenable to reverse genetics, we have generated induced pluripotent stem cell (IPSC) lines from prairie vole fibroblasts using retroviral transduction of reprogramming factors. These IPSC lines display the cellular and molecular hallmarks of IPSC cells from other organisms, including mice and humans. Moreover, the prairie vole IPSC lines have pluripotent differentiation potential since they can give rise to all three germ layers in tissue culture and in vivo. These IPSC lines can now be used to develop conditions that facilitate homologous recombination and eventually the generation of prairie voles bearing targeted genetic modifications to study the molecular and neural basis of pair bond formation.

Mate Selection, Sexual Orientation, and Pair Bonding

“…Bacterial artificial chromosome libraries have been developed and used to isolate many of the genes implicated in the pair bond process. 394 As more investigators utilize these tools, the growth in our understanding of the mechanisms of pair bonding shall continue on its impressive trajectory. 392 The prairie vole genome sequence has recently been made available on a public database.…”

Present and future challenges of induced pluripotent stem cells

“…The less invasive generation of iPSCs from somatic cells of rare animals facing extinction allows us to access their developmental processes. Thus far, iPSCs have been generated from, for example, a northern white rhino, drill monkey [113], snow leopard [114], domesticated horse [115] and prairie vole [116]. Such iPSCs from various bioresources should facilitate the understanding of species-specific molecular biology.…”

Neuropeptidergic regulation of pair-bonding and stress buffering: Lessons from voles

“…To our knowledge, at the present time, there are two labs attempting to generate transgenic prairie voles: one under the direction of Dr. Larry Young’s group at Emory University in Atlanta (Donaldson et al, 2009) and the second principal investigator Nirao Shah’s group at the University of California at San Francisco (Manoli et al, 2012). When a Cre/LOX (or similar transgenic prairie vole line is generated) - similar studies, as mentioned above, can commence.…”