Leukemia inhibitory factor (LIF)-dependent, pluripotent stem cells established from inner cell mass of porcine embryos

Autor: Andrei P. Alexenko, Randall S. Prather, Toshihiko Ezashi, Lee D. Spate, Bhanu Prakash V.L. Telugu, Sunilima Sinha, R. Michael Roberts
Rok vydání: 2011
Předmět:
KOSR
Pluripotent Stem Cells
Swine
Induced Pluripotent Stem Cells
Kruppel-Like Transcription Factors
KLF4
POU5F1
Embryoid body
Biology
Biochemistry
Leukemia Inhibitory Factor
Cell Line
Mesoderm
03 medical and health sciences
Kruppel-Like Factor 4
Mice
0302 clinical medicine
Species Specificity
Embryonic Stem Cell
Animals
Humans
Naive
Induced pluripotent stem cell
Molecular Biology
Embryonic Stem Cells
030304 developmental biology
0303 health sciences
Induced stem cells
Tetraploid complementation assay
Stem Cells
Cell Differentiation
Cell Biology
Cell Dedifferentiation
Embryonic stem cell
Antigens
Differentiation
3. Good health
Cell biology
Blastocyst
Embryo
Immunology
embryonic structures
Stem cell
Primed
Octamer Transcription Factor-3
030217 neurology & neurosurgery
Adult stem cell
Developmental Biology
Transcription Factors
Zdroj: The Journal of Biological Chemistry
ISSN: 1083-351X
Popis: The pig is important for agriculture and as an animal model in human and veterinary medicine, yet despite over 20 years of effort, there has been a failure to generate pluripotent stem cells analogous to those derived from mouse embryos. Here we report the production of leukemia inhibitory factor-dependent, so-called naive type, pluripotent stem cells from the inner cell mass of porcine blastocysts by up-regulating expression of KLF4 and POU5F1. The alkaline phosphatase-positive colonies resulting from reprogramming resemble mouse embryonic stem cells in colony morphology, cell cycle interval, transcriptome profile, and expression of pluripotent markers, such as POU5F1, SOX2, and surface marker SSEA1. They are dependent on leukemia inhibitory factor signaling for maintenance of pluripotency, can be cultured over extended passage, and have the ability to form teratomas. These cells derived from the inner cell mass of pig blastocysts are clearly distinct from the FGF2-dependent "primed" induced pluripotent stem cells described recently from porcine mesenchymal cells. The data are consistent with the hypothesis that the up-regulation of KLF4, as well as POU5F1, is required to create and stabilize the naive pluripotent state and may explain why the derivation of embryonic stem cells from pigs and other ungulates has proved so difficult.
Databáze: OpenAIRE
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