The new findings highlight the role of KLF4
, one of the transcription factors that gives stem cells their unique properties.
As they expected, the forced induction of four transcription factors (Yamanaka factors), Oct3/4, Sox2, Klf4
, and c-Myc, all of which are highly expressed and contribute to the maintenance of ESC identity, resulted in the generation of iPSCs (Fig.
Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4
with small-molecule compounds.
"[H]ere we demonstrate[d] induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4
, under ES cell culture conditions." Id.
These initial observations have been later completed by the identification of other genetic alterations, such as DAL-1, TRAF7, AKT1, KLF4
, PTCH1, SMARCE1, BAP1, SMO, and PIK3CA mutations [4, 5].
It has already been shown that c-Myc and Klf4
are sufficient to differentiate myocardial mesenchymal progenitors into adipocytes without the commonly used adipogenic stimulation cocktail (15).
Cluster 1 includes proteins CASP3, CASP9, BAX, TP53, BAD, GSK3B, POU5F1, MAPK14, CREB1, SOX2, and KLF4
. Gene ontology data show that these proteins are associated with amyotrophic lateral sclerosis (hsa05014) , colorectal cancer (hsa05210) , and positive regulation of neuron death (GO: 1901216) .
Yan et al., "KLF4
is essential for induction of cellular identity change and acinar-to-ductal reprogramming during early pancreatic carcinogenesis," Cancer Cell, vol.
iPSCs were artificially produced for the first time by Takahashi and Yamanaka through ectopic expression of Oct4, Sox2, Klf4
, and cMyc (together OSKM) in murine somatic cells  and by Thompson's group in human cells by replacing Klf4
and cMyc with factors LIN28 and NANOG .
, originally separated from the gastrointestinal tract, is one of the transcriptional regulation factors of adipocyte differentiation .
Webster et al., "ZNF750 is a p 63 target gene that induces KLF4
to drive terminal epidermal differentiation," Developmental Cell, vol.
Our previous review summarized that PPAR[gamma] inhibits cell proliferation and induces apoptosis through the upregulation of Phosphatase and Tensin Homolog (PTEN), downregulation of survivin, downregulation of X-linked inhibitor of apoptosis (XIAP), suppression of NF-[kappa]B and glycogen synthase kinase (GSK)-3[beta], upregulation of cyclin-dependent kinase (CDK) inhibitors, downregulation of CDK and cyclin D1, downregulation of COX-2, upregulation of Kruppel-Like Factor 4 (KLF4
), upregulation of Bax, downregulation of Bcl-2, and inhibition of telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network .