KLF4, Oct4 induce pluipotency in dermal papillae
Kofi
Oct4 and Klf4 Reprogram Dermal Papilla Cells into Induced Pluripotent
Stem Cells.
Tsai SY, Clavel C, Kim S, Ang YS, Grisanti L, Lee DF, Kelley K, Rendl M.
Black Family Stem Cell Institute, Mount Sinai School of Medicine, New
York, New York, USA.
Direct reprogramming of somatic cells into induced pluripotent stem
(iPS) cells by only four transcription factors (Oct4, Sox2, Klf4, c-Myc)
has great potential for tissue specific regenerative therapies,
eliminating the ethical issues surrounding the use of embryonic stem
cells (ES) cells and the rejection problems of using non-autologous
cells. The reprogramming efficiency generally is very low, however, and
the problems surrounding the introduction of viral genetic material are
only partially investigated. Recent efforts to reduce the number of
virally expressed transcription factors succeeded to reprogram neural
stem cells into iPS cells by overexpressing Oct4 alone. However, the
relative inaccessibility and difficulty of obtaining neural cells in
humans remains to be resolved. Here we report that dermal papilla (DP)
cells, which are specialized skin fibroblasts thought to instruct hair
follicle stem cells, endogenously express high levels of Sox2 and c-Myc,
and that these cells can be reprogrammed into iPS cells with only Oct4
and Klf4. Moreover, we show that DP cells are reprogrammed more
efficiently than skin and embryonic fibroblasts. iPS cells derived from
DP cells expressed pluripotency genes and differentiated into cells from
all germ layers in vitro and widely contributed to chimeric mice in
vivo, including the germline. Our work establishes DP cells as an easily
accessible source to generate iPS cells efficiently and with less
genetic material. This opens up the possibility of streamlined
generation of skin-derived, patient-specific pluripotent stem cells and
of ultimately replacing the remaining two factors with small molecules
for safe generation of transplantable cells.
PMID: 20014278
ghrelin & Kruppel-like factor 4 (KLF4) are both expressed in the
stomach; ghrelin is elevated by fasting and by KLF4; butyrate induces
both ghrelin and KLF4; KLF4 expression specifically stimulates human
ghrelin promoter activity in a dose-dependent manner by binding to a KLF
domain on the promoter [PMID 19327128]