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IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro
Oleh:
Bendall, Sean C.
;
Stewart, Morag H.
;
Menendez, Pablo
;
Dustin, George
;
Vijayaragavan, Kausalia
;
and Others
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
NATURE (keterangan: ada di Proquest) vol. 448 no. 7157 (Aug. 2007)
,
page 1015.
Ketersediaan
Perpustakaan FK
Nomor Panggil:
N01.K.2007.08
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
Distinctive properties of stem cells are not autonomously achieved, and recent evidence points to a level of external control from the microenvironment. Here, we demonstrate that self-renewal and pluripotent properties of human embryonic stem (ES) cells depend on a dynamic interplay between human ES cells and autologously derived human ES cell fibroblast-like cells (hdFs). Human ES cells and hdFs are uniquely defined by insulin-like growth factor (IGF)- and fibroblast growth factor (FGF)-dependence. IGF 1 receptor (IGF1R) expression was exclusive to the human ES cells, whereas FGF receptor 1 (FGFR1) expression was restricted to surrounding hdFs. Blocking the IGF-II/IGF1R pathway reduced survival and clonogenicity of human ES cells, whereas inhibition of the FGF pathway indirectly caused differentiation. IGF-II is expressed by hdFs in response to FGF, and alone was sufficient in maintaining human ES cell cultures. Our study demonstrates a direct role of the IGF-II/IGF1R axis on human ES cell physiology and establishes that hdFs produced by human ES cells themselves define the stem cell niche of pluripotent human stem cells.
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