September 27, 2011 (last updated: November 9, 2011)
For more information select an underlined item
It is a well-known fact that several molecules play important roles in the self-renewal and pluripotency of ES cells and iPSCs. These molecules regulate various cells functions such as cell cycle, transcription and so on. Certainly, the elucidation of interactions between these molecules may contribute to understanding the transformations of cells (differentiation and induced pluripotency). Bellow, you can see a list of molecules involved in self-renewal and pluripotency of ES cells and iPSCs. Sure, this list is not complete.
For more information select an underlined item
It is a well-known fact that several molecules play important roles in the self-renewal and pluripotency of ES cells and iPSCs. These molecules regulate various cells functions such as cell cycle, transcription and so on. Certainly, the elucidation of interactions between these molecules may contribute to understanding the transformations of cells (differentiation and induced pluripotency). Bellow, you can see a list of molecules involved in self-renewal and pluripotency of ES cells and iPSCs. Sure, this list is not complete.
1. Proteins
1.1 Transcription factors
Master stem cell transcription factors
Nanog - Nanog homeobox
Oct4 (POU5F1) - POU class5 homeobox1
Sox2 (SRY) - sex determining region Y-box2
Stem cell transcription factors
CTCF - CCCTC-binding factor (zinc finger protein)
E2f1 - E2F transcription factor1
Esrrb - estrogen-related receptor beta
Gli-like transcription factor Glis1 - Glis family zinc finger1
E2f1 - E2F transcription factor1
Esrrb - estrogen-related receptor beta
Gli-like transcription factor Glis1 - Glis family zinc finger1
HoxB1 - homeobox protein B1
Klf4 - Krüppel-like factor4
c-Myc (c-Myc, v-Myc, MRTL, bHLHe39) and n-Myc. Myelocytomatosis viral oncogene, c-Myc by overexpression activates of TERT, RNA polymerase III, HSP90A, p21, p53.
Nac1 (NACC1, BTB/POZ domain-containing protein 14B) nucleus accumbens- associated protein
Neurog1 - neurogenin1
Nkx2-2 - Nk2 homeobox2
Osr2 - protein odd-skipped related2
Pax6 - paired box6
Pem (now called Rhox5) blocks the in vitro and in vivo differentiation of the cells
REX1 (ZFP42) - acidic zinc-finger protein42
Pax6 - paired box6
Pem (now called Rhox5) blocks the in vitro and in vivo differentiation of the cells
REX1 (ZFP42) - acidic zinc-finger protein42
Sall4 - Sal-like protein4
Spic - Spi-C transcription factor
Suz12 - suppresor of zeste 12 homolog (Drosophila)
Tcfcp2l1 - transcription factor CP2-like1
Suz12 - suppresor of zeste 12 homolog (Drosophila)
Tcfcp2l1 - transcription factor CP2-like1
Zfp281 - zinc finger protein281
Zfp36L1 - zinc finger protein 36, C3H type-like1
Zfx - zinc finger protein, X-linked
Zfx - zinc finger protein, X-linked
ZIC3 - zinc finger protein Zic3
1.2 Binding proteins
Lin28 - Lin28 homolog A is a RNA binding protein
REST - RE1-silencing transcription factor is a RNA binding protein
Rif1 - telomere-associated protein Rif1 is a telomeric DNA binding protein
Id-1 and Id-2 (BMP4/Smad pathway) - DNA binding protein inhibitors Id-1 and Id-2 (or inhibitors of differentiation) that inhibit gene expression in multiple cells
Id-1 and Id-2 (BMP4/Smad pathway) - DNA binding protein inhibitors Id-1 and Id-2 (or inhibitors of differentiation) that inhibit gene expression in multiple cells
1.3 Cell receptors
bFGFRs (FGF pathway) four basic fibroblast growth factor receptors
Dax1 is nuclear receptor subfamily 0, group B, membre1
Dax1 is nuclear receptor subfamily 0, group B, membre1
ERRb (ERR2) estrogen related receptor beta
Gpl30 is interleukin 6 receptor-associated signal transducer (LIF-STAT3 pathway)
IGF1R - IGF1 receptor
LIFR (CD118) is leukemia inhibitory factor receptor
Nr5a2 (also known Lrh-1) orphan nuclear receptor that can remplace Oct4 in the derivation of iPSCs from mouse somatic cells
SCF/KitR (SCF/Kit pathway) - stem cell factor and Kit receptor
Gpl30 is interleukin 6 receptor-associated signal transducer (LIF-STAT3 pathway)
IGF1R - IGF1 receptor
LIFR (CD118) is leukemia inhibitory factor receptor
Nr5a2 (also known Lrh-1) orphan nuclear receptor that can remplace Oct4 in the derivation of iPSCs from mouse somatic cells
SCF/KitR (SCF/Kit pathway) - stem cell factor and Kit receptor
1.4 Signalling molecules (signal transducer activity)
The processes involved in maintaining the embryonic state and in generating of induced pluripotent stem cells (iPSCs) are regulated by multiple interactions between cellular signalling molecules. In addition, cell differentiation is coordinated by the same interactions. Signalling molecules belong to several cellular pathways: (1) LIF-STAT3, (2) MAPK-ERK (p42/p44 MAPK), (3) PI3K, (4) Wnt, (5) TGFβ, (6) bFGF and probably others.
EGF (EGF pathway) - epidermal growth factor that stimulates cell divisions by induced DNA synthesis (PLC/PKC protein kinase C, Ca2+ influx and ERK1/2 pathway) and by incresed cell metabolism (GLUT1)
bFGF (probably by MAPK signaling, bFGF pathway) basic fibroblast growth factor
DKK1 (Wnt pathway) - dickkopf-related protein1
FRAT2 (Wnt pathway) - GSK-3-binding protein
IGFs (IGF pathways) - insulin-like growth factors (IGF1 and IGF2)
IRS1 (IGF pathways) - insulin receptor substrat 1
IGFs (IGF pathways) - insulin-like growth factors (IGF1 and IGF2)
IRS1 (IGF pathways) - insulin receptor substrat 1
Lefty/EBAF (TGF-β pathway): Lefty - left-right determination factor and EBAF - endometrial bleeding-associated factor
NTs - neurotrophins with role in hES cell survival
p53 (TP53 in human or Trp53 in mouse): p53-p21 patway is a barrier in iPSCs generation
SKIL - SKI-like oncogene
NTs - neurotrophins with role in hES cell survival
p53 (TP53 in human or Trp53 in mouse): p53-p21 patway is a barrier in iPSCs generation
SKIL - SKI-like oncogene
SMADs (BMP4 pathway) - SMAD family proteins
STAT3 - signal transducer and activator of transcription 3 (LIF-STAT3 and Wnt-STAT3 pathways may converge c-Myc, Klf4, Pramel7)
TDGF1 (TGF-β pathway) - teratocarcinoma-derived growth factor1
1.5 Enzymes
AKT or PKB (PI3K pathway) is a serine/treonine protein kinase
ERKs (by LIF) - extracellular signal-regulated kinase
1.5 Enzymes
AKT or PKB (PI3K pathway) is a serine/treonine protein kinase
ERKs (by LIF) - extracellular signal-regulated kinase
FGF (FGF pathway) - fibroblast growth factor
JAKs (LIF-STAT3 pathway) - Janus-associated tyrosine kinase
MAPK-ERK (MAPK-ERK parhway) - mitogen-activated protein kinase
PI3K (PI3K pathway) - phosphoinositide 3-kinase
Src family kinase (Src family pathway): Hck, Lck, Lyn, Yes
JAKs (LIF-STAT3 pathway) - Janus-associated tyrosine kinase
MAPK-ERK (MAPK-ERK parhway) - mitogen-activated protein kinase
PI3K (PI3K pathway) - phosphoinositide 3-kinase
Src family kinase (Src family pathway): Hck, Lck, Lyn, Yes
2. micro RNA
Let-7 microRNA
Sources:
1. Annerén, C. (2008) Tyrosine kinase signalling in embryonic stem cells. Clinical Science. 115, 43-55.
6. Kashyap, V. et al. (2009) Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells Dev. 7, 1093-1108.
1. Annerén, C. (2008) Tyrosine kinase signalling in embryonic stem cells. Clinical Science. 115, 43-55.
2. Azevedo, JL. and Feldman, RA. (2010) Tinkering with Transcription Factors Uncovers Plasticity of Somatic Cells. Genes Cancer. 1, 1089-99.
3. Ben-Sushan, E. et al. (1998) Rex-1, a Gene Encoding a Transcription Factor Expressed in the Early Embryo, Is Regulated via Oct-3/4 and Oct-6 Binding to an Octomer Site and a Novel Protein, Rox-1, Binding to an Adjacent Site. Moll Cell Biol. 18, 1866-78.
4. Casanova, EA. et al. (2011) Pramel7 Mediates LIF/STAT3 Dependent Self-Renewal in embryonic Stem Cells. Stem Cells. 29, 474-85.
5. Hong, H. et al. (2009) Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature. 460, 1132-35.
5. Hong, H. et al. (2009) Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature. 460, 1132-35.
6. Kashyap, V. et al. (2009) Regulation of stem cell pluripotency and differentiation involves a mutual regulatory circuit of the NANOG, OCT4, and SOX2 pluripotency transcription factors with polycomb repressive complexes and stem cell microRNAs. Stem Cells Dev. 7, 1093-1108.
7. Liu, N. et al. (2006) Molecular mechanisms involved in self-renewal and pluripotency of embryonic stem cells. J Cell Physiol. 211, 279-286.
8. Orkin, S.H. et al. (2008) The transcriptional network controlling pluripotency in ES cells. Cold Spring Harb Symp Quant Biol. 73, 195-202.
9. Scheper, W. and Copray, S. (2009) The molecular mechanism of induced pluripotency: a two-stage switch. Stem Cell Rev. 5, 204-23.
10. Teng, SC. et al. Direct activation of HSP90A Transcription by c-Myc Contributes to c-Myc-induced Transformation. J. Biol. Chem. 279, 14649-55.
11. Wu, KJ. et al. (1999) Direct activation of TERT transcription by c-Myc. Nature Genetics. 21, 220-24.
