EMAIL THIS PAGE TO A FRIEND

Stem cells (Dayton, Ohio)

Signalling Through Retinoic Acid Receptors is Required for Reprogramming of Both Mouse Embryonic Fibroblast Cells and Epiblast Stem Cells to Induced Pluripotent Stem Cells.


PMID 25546009

Abstract

We previously demonstrated that coexpressing retinoic acid (RA) receptor gamma and liver receptor homolog-1 (LRH1 or NR5A2) with OCT4, MYC, KLF4, and SOX2 (4F) rapidly reprograms mouse embryonic fibroblast cells (MEFs) into induced pluripotent stem cells (iPSCs). Here, we further explore the role of RA in reprogramming and report that the six factors (6F) efficiently and directly reprogram MEFs into integration-free iPSCs in defined medium (N2B27) in the absence of feeder cells. Through genetic and chemical approaches, we find that RA signalling is essential, in a highly dose-sensitive manner, for MEF reprogramming. The removal of exogenous RA from N2B27, the inhibition of endogenous RA synthesis or the expression of a dominant-negative form of RARA severely impedes reprogramming. By contrast, supplementing N2B27 with various retinoids substantially boosts reprogramming. In addition, when coexpressed with LRH1, RA receptors (RARs) can promote reprogramming in the absence of both exogenous and endogenously synthesized RA. Remarkably, the reprogramming of epiblast stem cells into embryonic stem cell-like cells also requires low levels of RA, which can modulate Wnt signalling through physical interactions of RARs with β-catenin. These results highlight the important functions of RA signalling in reprogramming somatic cells and primed stem cells to naïve pluripotency. Stem Cells 2015;33:1390-1404.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

AV100591
Anti-NANOG (AB1) antibody produced in rabbit, affinity isolated antibody
AV47988
Anti-NANOG (AB2) antibody produced in rabbit, affinity isolated antibody
SAB2500670
Anti-NANOG antibody produced in goat, affinity isolated antibody, buffered aqueous solution
N4413 Anti-Nanog antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB4300680
Anti-Nanog antibody produced in rabbit, affinity isolated antibody
SAB3500389
Anti-NANOG antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2104002
Anti-NANOG antibody produced in rabbit, affinity isolated antibody
SAB2104004
Anti-NANOG, (N-terminal) antibody produced in rabbit, affinity isolated antibody
SAB2500671
Anti-NANOG, C-Terminal antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2101947
Anti-RARG antibody produced in rabbit, affinity isolated antibody
SAB2103974
Anti-RARG antibody produced in rabbit, affinity isolated antibody
HPA053883
Anti-RARG antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1406371
Anti-RARG, (N-terminal) antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
C5865
CD437, ≥98% (HPLC), solid
C27H26O3
W230316
Citral, natural, ≥96%, FCC, FG
C10H16O
C83007
Citral, 95%
C10H16O
43318
Citral, analytical standard
C10H16O
W230308
Citral, mixture of cis and trans, ≥96%, FG
C10H16O
I0161
IWR-1, ≥98% (HPLC)
C25H19N3O3
N3038
Monoclonal Anti-Nanog antibody produced in mouse, ~2 mg/mL, clone NNG-811, purified immunoglobulin, buffered aqueous solution
WH0079923M1
Monoclonal Anti-NANOG antibody produced in mouse, clone 2C11, purified immunoglobulin, buffered aqueous solution
SAB1405280
Monoclonal Anti-NANOG antibody produced in mouse, clone 2E11, purified immunoglobulin, buffered aqueous solution
R7632
Retinol, synthetic, ≥95% (HPLC), crystalline
C20H30O
95144
Retinol, BioXtra, ≥97.5% (HPLC), ~3100 U/mg
C20H30O
17772
Retinol, ≥95.0% (HPLC), ~2700 U/mg
C20H30O
PHR1187
Tretinoin, Pharmaceutical Secondary Standard; Certified Reference Material
C20H28O2
1674004
Tretinoin, United States Pharmacopeia (USP) Reference Standard
C20H28O2
T1850000
Tretinoin, European Pharmacopoeia (EP) Reference Standard
C20H28O2