Biomaterial Database

Inducing Pluripotency in the Domestic Cat (Felis catus). 2019

Luke C Dutton, and Jayesh Dudhia, and Deborah J Guest, and David J Connolly

Department of Clinical Science and Services, Royal Veterinary College, University of London, Hatfield, United Kingdom.

Domestic cats suffer from a range of inherited genetic diseases, many of which display similarities with equivalent human conditions. Developing cellular models for these inherited diseases would enable drug discovery, benefiting feline health and welfare as well as enhancing the potential of cats as relevant animal models for translation to human medicine. Advances in our understanding of these diseases at the cellular level have come from the use of induced pluripotent stem cells (iPSCs). iPSCs can differentiate into virtually any cell type and can be derived from adult somatic cells, therefore overcoming the ethical implications of destroying embryos to obtain embryonic stem cells. No studies, however, report the generation of iPSCs from domestic cats [feline iPSCs (fiPSCs)]. Feline adipose-derived fibroblasts were infected with amphotropic retrovirus containing the coding sequences for human Oct4, Sox2, Klf4, cMyc, and Nanog. Isolated iPSC clones were expanded on inactivated mouse embryonic fibroblasts in the presence of feline leukemia inhibitory factor (fLIF). Retroviral delivery of human pluripotent genes gave rise to putative fiPSC colonies within 5-7 days. These iPS-like cells required fetal bovine serum and fLIF for maintenance. Colonies were domed with refractile edges, similar to mouse iPSCs. Immunocytochemistry demonstrated positive staining for stem cell markers: alkaline phosphatase, Oct4, Sox2, Nanog, and SSEA1. Cells were negative for SSEA4. Expression of endogenous feline Nanog was confirmed by quantitative polymerase chain reaction. The cells were able to differentiate in vitro into cells representative of the three germ layers. These results confirm the first generation of induced pluripotent stem cells from domestic cats. These cells will provide valuable models to study genetic diseases and explore novel therapeutic strategies.

UI	MeSH Term	Description	Entries
D008979	Moloney murine leukemia virus	A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.	Moloney Leukemia Virus,Leukemia Virus, Moloney,Virus, Moloney Leukemia
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005822	Genetic Vectors	DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.	Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071317	Nanog Homeobox Protein	A homeodomain protein and transcription regulator that functions in BLASTOCYST INNER CELL MASS and EMBRYONIC STEM CELL proliferation and CELL SELF RENEWAL. It confers pluripotency on embryonic stem cells and prevents their differentiation towards extraembryonic ENDODERM and trophectoderm (TROPHOBLAST) CELL LINEAGES.	Nanog Homeobox Transcription Factor,Nanog Protein,Homeobox Protein, Nanog
D000090062	Kruppel-Like Factor 4	A member of zinc finger-containing transcription factors that belongs to the KRUPPEL-LIKE FACTOR family, involved in the regulation of diverse cellular processes such as cell growth, proliferation, differentiation, and APOPTOSIS.	EZF Protein,Endothelial Kruppel-Like Zinc Finger Protein,Epithelial Zinc Finger Protein,GKLF Protein,Gut-Enriched Kruppel-Like Factor,Klf4 Protein,Krueppel-Like-Factor 4,4, Krueppel-Like-Factor,4, Kruppel-Like Factor,Endothelial Kruppel Like Zinc Finger Protein,Factor 4, Kruppel-Like,Factor, Gut-Enriched Kruppel-Like,Gut Enriched Kruppel Like Factor,Kruppel Like Factor 4,Protein, EZF,Protein, GKLF,Protein, Klf4
D000273	Adipose Tissue	Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.	Fatty Tissue,Body Fat,Fat Pad,Fat Pads,Pad, Fat,Pads, Fat,Tissue, Adipose,Tissue, Fatty