https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/159777/1/j.cell.2006.07.024.pdf

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/49782/1/Yamanaka_Cell_131_5.pdf

Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors

Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that dismantle the cell. More distant relatives instead promote apoptosis, apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not all apoptotic signals, the balance between these competing activities determines cell fate. Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in cancer.

https://science.sciencemag.org/content/sci/281/5381/1322.full.pdf

The Bcl-2 Protein Family: Arbiters of Cell Survival

CA : A Cancer Journal for Clinicians

If it were possible to reprogram differentiated human somatic cells into a pluripotent state, patient-specific and disease-specific stem cells could be developed. Previous work generated induced pluripotent stem (iPS) cells capable of germline transmission from murine somatic cells by transd

/pdf/induction-of-pluripotent-stem-cells-from-adult-human-3jc4cxk5x5.pdf

Induction of Pluripotent Stem Cells From Adult Human Fibroblasts by Defined Factors

Cytokines: Coordinators of Immune and Inflammatory Responses

Embryonic stem (ES) cells can be maintained in an undifferentiated state in the presence of leukemia inhibitory factor (LIF). LIF acts through a receptor complex composed of a low affinity LIF receptor (LIFRbeta) and gp130. We reported that the intracellular domain of gp130 plays an important role in self-renewal of ES cells. In the present study, we examined the signaling pathway through which gp130 contributes to the self-renewal of ES cells. Mutational analysis of the cytoplasmic domain of gp130 revealed that the tyrosine residue of gp130 responsible for STAT3 activation is necessary for self-renewal of ES cells, while that required for SHP2 and MAP kinase activation was dispensable. Next, we constructed a fusion protein composed of the entire coding region of STAT3 and the ligand binding domain of the estrogen receptor. This construction (STAT3ER) induced expression of junB (one of the targets of STAT3) in ES cells in the presence of the synthetic ligand 4-hydroxytamoxifen (4HT), thereby indicating that STAT3ER is a conditionally active form. ES cells transfected with STAT3ER cultured in the presence of 4HT maintained an undifferentiated state. Taken together, these results strongly suggest that STAT3 activation is required and sufficient to maintain the undifferentiated state of ES cells.

/pdf/stat3-activation-is-sufficient-to-maintain-an-1bhi81y3jb.pdf

STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells

Using the mouse interleukin 3 (IL-3) receptor cDNA as a probe, we obtained a homologous cDNA (KH97) from a cDNA library of a human hemopoietic cell line, TF-1. The protein encoded by the KH97 cDNA has 56% amino acid sequence identity with the mouse IL-3 receptor and retains features common to the family of cytokine receptors. Fibroblasts transfected with the KH97 cDNA expressed a protein of 120 kDa but did not bind any human cytokines, including IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, cotransfection of cDNAs for KH97 and the low-affinity human GM-CSF receptor in fibroblasts resulted in formation of a high-affinity receptor for GM-CSF. The dissociation rate of GM-CSF from the reconstituted high-affinity receptor was slower than that from the low-affinity site, whereas the association rate was unchanged. Cross-linking of 125I-labeled GM-CSF to fibroblasts cotransfected with both cDNAs revealed the same cross-linking patterns as in TF-1 cells--i.e., two major proteins of 80 and 120 kDa which correspond to the low-affinity GM-CSF receptor and the KH97 protein, respectively. These results indicate that the high-affinity GM-CSF receptor is composed of at least two components in a manner analogous to the IL-2 receptor. We therefore propose to designate the low-affinity GM-CSF receptor and the KH97 protein as the alpha and beta subunits of the GM-CSF receptor, respectively.

https://www.pnas.org/content/pnas/87/24/9655.full.pdf

Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor.

Cytokines play a vital role in coordinating immune and inflammatory re­ sponses. Unlike growth factor receptors with a tyrosine kinase, cytokine receptors have no intrin sic tyrosine kinase activity. Based on their struc­ ture, cytokine receptors are classified into several groups. High affinity recep­ tors for IL-2, IL-3, IL-5, IL-6, and GM-CSF are composed of at least two distin ct subunits, C( and {3. The C( subunits are primary cytokine binding proteins, and the {3 subunits are required for for mation of high affinity

Cytokine receptors and signal transduction

SALL1 is a mammalian homolog of the Drosophila 

region-specific homeotic gene spalt ( sal ); heterozygous

mutations in SALL1 in humans lead to Townes-Brocks syndrome. We have

isolated a mouse homolog of SALL1 ( Sall1 ) and found that

mice deficient in Sall1 die in the perinatal period and that kidney

agenesis or severe dysgenesis are present. Sall1 is expressed in the

metanephric mesenchyme surrounding ureteric bud; homozygous deletion of

 Sall1 results in an incomplete ureteric bud outgrowth, a failure of

tubule formation in the mesenchyme and an apoptosis of the mesenchyme. This

phenotype is likely to be primarily caused by the absence of the inductive

signal from the ureter, as the Sall1 -deficient mesenchyme is

competent with respect to epithelial differentiation. Sall1 is

therefore essential for ureteric bud invasion, the initial key step for

metanephros development.

/pdf/murine-homolog-of-sall1-is-essential-for-ureteric-bud-5g4ystt8jb.pdf

Takashi Yokota

Papers

Cytokines: Coordinators of Immune and Inflammatory Responses

STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells

Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor.

Cytokine receptors and signal transduction

Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development.