Generation of Naive-like Porcine-induced Pluripotent Stem Cells Capable of Contributing to Embryonic and Fetal Development

Overview

Journal Stem Cells Dev

Date 2012 Aug 15

PMID 22889279

Citations 64

Authors

Shuh-Hei Fujishiro

Kazuaki Nakano

Yoshihisa Mizukami

Takuya Azami

Yoshikazu Arai

Hitomi Matsunari

Rikiya Ishino

Takashi Nishimura

Masahito Watanabe

Tomoyuki Abe

Yutaka Furukawa

Kazuhiro Umeyama

Shinya Yamanaka

Masatsugu Ema

Hiroshi Nagashima

Yutaka Hanazono

Affiliations

Soon will be listed here.

Abstract

In pluripotent stem cells (PSCs), there are 2 types: naive and primed. Only the naive type has the capacity for producing chimeric offspring. Mouse PSCs are naive, but human PSCs are in the primed state. Previously reported porcine PSCs appear in the primed state. In this study, putative naive porcine-induced pluripotent stem cells (iPSCs) were generated. Porcine embryonic fibroblasts were transduced with retroviral vectors expressing Yamanaka's 4 genes. Emergent colonies were propagated in the presence of porcine leukemia inhibitory factor (pLIF) and forskolin. The cells expressed pluripotency markers and formed embryoid bodies, which gave rise to cell types from all 3 embryonic germ layers. The naive state of the cells was demonstrated by pLIF dependency, 2 active X chromosomes (when female), absent MHC class I expression, and characteristic gene expression profiles. The porcine iPSCs contributed to the in vitro embryonic development (11/24, 45.8%) as assessed by fluorescent markers. They also contributed to the in utero fetal development (11/71, 15.5% at day 23; 1/13, 7.7% at day 65). This is the first demonstration of macroscopic fluorescent chimeras derived from naive-like porcine PSCs, although adult chimeras remain to be produced.

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