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Reprogramming of rabbit induced pluripotent stem cells toward epiblast and chimeric competency using Krüppel-like factors.

Abstract：

:Rabbit induced pluripotent stem cells (rbiPSCs) possess the characteristic features of primed pluripotency as defined in rodents and primates. In the present study, we reprogrammed rbiPSCs using human Krüppel-like factors (KLFs) 2 and 4 and cultured them in a medium supplemented with fetal calf serum and leukemia inhibitory factor. These cells (designated rbEKA) were propagated by enzymatic dissociation for at least 30 passages, during which they maintained a normal karyotype. This new culturing protocol resulted in transcriptional and epigenetic reconfiguration, as substantiated by the expression of transcription factors and the presence of histone modifications associated with naïve pluripotency. Furthermore, microarray analysis of rbiPSCs, rbEKA cells, rabbit ICM cells, and rabbit epiblast showed that the global gene expression profile of the reprogrammed rbiPSCs was more similar to that of rabbit ICM and epiblast cells. Injection of rbEKA cells into 8-cell stage rabbit embryos resulted in extensive colonization of ICM in 9% early-blastocysts (E3.5), epiblast in 10% mid-blastocysts (E4.5), and embryonic disk in 1.4% pre-gastrulae (E6). Thus, these results indicate that KLF2 and KLF4 triggered the conversion of rbiPSCs into epiblast-like, embryo colonization-competent PSCs. Our results highlight some of the requirements to achieve bona fide chimeric competency.

journal_name

Stem Cell Res

journal_title

Stem cell research

authors

Tapponnier Y,Afanassieff M,Aksoy I,Aubry M,Moulin A,Medjani L,Bouchereau W,Mayère C,Osteil P,Nurse-Francis J,Oikonomakos I,Joly T,Jouneau L,Archilla C,Schmaltz-Panneau B,Peynot N,Barasc H,Pinton A,Lecardonnel J,Gocz

doi

10.1016/j.scr.2017.09.001

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

106-117

eissn

1873-5061

issn

1876-7753

pii

S1873-5061(17)30185-X

journal_volume

24

pub_type

杂志文章

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