Ectopic expression of four transcription factors including Oct4, Sox2, Klf4 and c-Myc in differentiated fibroblast cells could reset the cell fate of fibroblast cells to pluripotent state. Subsequently, fully pluripotency of these so-called induced pluripotent stem cells (iPSCs) has been demonstrated as viable mice could be generated autonomously from iPS cells through tetraploid blastocyst complementation. Moreover, the generation of human and patient-specific iPS cells have raised the possibility of utilizing iPS cells clinically. However, the utilization of c-Myc in iPS cells induction greatly increased the incidence of tumorigenecity in the iPS-chimeric mice and also might hinder the clinical application of human iPS cells in the future. Fortunately, c-Myc has been recently found dispensable for iPS induction even though the iPS induction efficiency is greatly reduced in the absence of c-Myc. However, it remains unknown if these three factors-induced iPS cells are fully pluripotent. In the present study, we have successfully demonstrated that 3-factor iPS cells could also be fully pluripotent as viable mice could be generated from 3-factor iPS cells autonomously via tetraploid complementation and moreover, our data indicated that the pluripotency regulatory mechanism in 3-factor iPS cells might be distinct from 4-factor iPS cells.
Viable mice produced from three-factor induced pluripotent stem (iPS) cells through tetraploid complementation.
Specimen part
View SamplesDifferentiated somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by forced expression of four transcription factorsOct4, Sox2, Klf4, and c-Myc. However, it remains undetermined whether the reprogrammed iPS cells are fully pluripotent, resembling normal embryonic stem (ES) cells, given that no iPS cell lines have been shown to possess the capability to autonomously generate full-term mice after injection into tetraploid blastocysts. Here, we provide evidence demonstrating that iPS cells induced by the four transcription factors can be fully pluripotent and that full-term mice can be produced from complemented tetraploid blastocysts. This work serves as a proof of principle that iPS cells can generate full term embryos by tetraploid complementation.
iPS cells can support full-term development of tetraploid blastocyst-complemented embryos.
Specimen part, Cell line
View SamplesDocetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors, however its toxicity and side-effect limits its clinical efficacy. Herein, the docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity while still keeping its anti-cancer activity. To evaluate its anti-cancer activity and toxicity and understand the molecular mechanisms of DSNs, different cellular, molecular and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel-Taxotere and induced more apoptosis at 24 h treatment in vitro. It can cause the treated cancer cells arrested at G2/M phase in a dose-depend manner as Taxotere. The DSNs can also suppress tumor growth very effectively in a murine breast cancer model. Systemic analysis of gene expression profiles by microarray and the following verification experiments suggested that both DSNs and Taxotere regulate expression of series genes and these genes functions involved in DNA replication, DNA damage response, cell proliferation, apoptosis and cell cycle regulation. Some of these genes expressed differentially at protein level although their transcription level was similar under TAX and DSNs treatment. Moreover, DSNs improved main side-effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, our results expound the anti-tumor efficacy and the potential working mechanisms of DSNs in its anti-cancer activity and toxicity, which provide a theoretical foundation to develop and apply more efficient docetaxel formulation to treat cancer patients.
Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity.
Specimen part
View SamplesProliferation and migration of lymphatic endothelial cells (LECs) are essential for lymphatic vessel growth (also known as lymphangiogenesis), which plays a critical role in regulating the tissue fluid balance and immune cell trafficking in physiological and pathological conditions.
Angiotensin II Stimulates the Proliferation and Migration of Lymphatic Endothelial Cells Through Angiotensin Type 1 Receptors.
Specimen part, Treatment
View SamplesAdoptive natural regulatory T cell (nTreg) therapy has improved the outcome for patients suffering from graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). However, fear of broad immune suppression and subsequent dampening of beneficial graft-versus-leukemic (GVL) responses remains a challenge. To address this concern, we generated alloreactive induced Tregs (iTregs) from resting CD4 or CD8 T cells and tested their ability to suppress GVH and maintain GVL responses. We utilized major mismatched and haploidentical murine models of HCT with host-derived lymphoma or leukemia cell lines to evaluate GVH and GVL responses simultaneously. Alloreactive CD4 iTregs were effective in preventing GVHD, but abrogated the GVL effect against aggressive leukemia. Alloreactive CD8 iTregs moderately attenuated GVHD while sparing the GVL effect. Hence, we reasoned that using a combination of CD4 and CD8 iTregs could achieve the optimal goal of allo-HCT. Indeed, the combinational therapy was superior to CD4 or CD8 iTreg singular therapy in GVHD control; importantly, the combinational therapy maintained GVL responses. Cellular analysis uncovered potent suppression of both CD4 and CD8 effector T cells by the combinational therapy that resulted in effective prevention of GVHD, which could not be achieved by either singular therapy. Gene expression profiles revealed alloreactive CD8 iTregs possess elevated expression of multiple cytolytic molecules compared to CD4 iTregs, which likely contributes to GVL preservation. Our study uncovers unique differences between alloreactive CD4 and CD8 iTregs that can be harnessed to create an optimal iTreg therapy for GVHD prevention with maintained GVL responses.
No associated publication
Specimen part, Treatment
View SamplesBiomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival.
COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer.
Specimen part
View SamplesMicroarray analysis of dithranol-treated psoriasis lesions before, during and after therapy
Dithranol targets keratinocytes, their crosstalk with neutrophils and inhibits the IL-36 inflammatory loop in psoriasis.
Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated genomics has identified a new AT/RT-like yet INI1-positive brain tumor subtype among primary pediatric embryonal tumors.
Sex, Specimen part, Disease, Disease stage
View SamplesFasting is the process of metabolic adaption to food deprivation that is taking place in most organisms, e.g. during the daily resting phase in mammals. Furthermore, in biomedical research fasting is used in most metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular players in fasting. In this study we investigated the transcriptome signature of white adipose tissue, liver, and skeletal muscle in 24 hours fasted mice (and chow fat controls) using Affymetrix whole-genome microarrays.
Metabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues.
Sex, Specimen part
View SamplesCancer cells express different sets of receptor type tyrosine kinases. These receptor kinases may be activated through autocrine or paracrine mechanisms. Fibroblasts may modify the biologic properties of surrounding cancer cells through paracrine mechansms.
The role of HGF/MET and FGF/FGFR in fibroblast-derived growth stimulation and lapatinib-resistance of esophageal squamous cell carcinoma.
Specimen part, Cell line
View Samples