• CRISPR/cas
• ISGylation
• NF-kappa B
• RIGI-like receptor
• dsRNA
• fallopian tube cells
• inflammation
• innate immunity
• interferon
• ovarian cancer

• Humans
• Female
• Fallopian Tubes/metabolism
• Fallopian Tubes/cytology
• Fallopian Tubes/pathology
• NF-kappa B/metabolism
• Signal Transduction
• Ubiquitins/metabolism
• Ubiquitins/genetics
• Epithelial Cells/metabolism
• Cytokines/metabolism
• Interferon Regulatory Factor-3/metabolism
• Interferon Regulatory Factor-3/genetics
• RNA, Double-Stranded/metabolism
• Membrane Proteins/metabolism
• Membrane Proteins/genetics
• Interferon-Induced Helicase, IFIH1/metabolism
• Interferon-Induced Helicase, IFIH1/genetics
• DEAD Box Protein 58/metabolism
• DEAD Box Protein 58/genetics
• BRCA1 Protein/metabolism
• BRCA1 Protein/genetics
• Nucleotidyltransferases/metabolism
• Nucleotidyltransferases/genetics
• Receptors, Immunologic/metabolism
• Receptors, Immunologic/genetics

• cancer models
• cancer stem cells
• paediatric cancer

• Neoplastic Stem Cells/pathology
• Neoplastic Stem Cells/metabolism
• Humans
• Animals
• Glioma/pathology
• Glioma/immunology
• Glioma/metabolism
• Neoplasm Invasiveness
• Mice
• Brain Neoplasms/pathology
• Brain Neoplasms/immunology
• Brain Neoplasms/metabolism
• CD57 Antigens/metabolism
• Child
• AC133 Antigen/metabolism

• R01 CA185402 NCI NIH HHS
• 32100563 National Natural Science Foundation of China (National Science Foundation of China)
• CA185402 U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health)
• 8217112078 National Natural Science Foundation of China (National Science Foundation of China)
• Childhood Brain Tumor Foundation (Childhood Brain Tumor Foundation, Inc.)
• U.S. Department of Health & Human Services | NIH | Center for Information Technology (Center for Information Technology, National Institutes of Health)

• NANOG
• OCT4
• PI3K/AKT
• RNAi
• TMZ
• cancer stem cells
• glioblastoma
• stemness genes

• Parasite cyst formation process
• Pediatric hydatidosis
• TGF-β/Smads/leukemia inhibitory factors (LIF) signaling pathway

• Animals
• Cell Differentiation
• Embryonic Stem Cells/metabolism
• Immunity, Innate
• Mice
• Mouse Embryonic Stem Cells

• P20 GM103476 NIGMS NIH HHS
• R15 GM109299 NIGMS NIH HHS
• R15 GM128196 NIGMS NIH HHS

During mammalian preimplantation development, as the fertilized egg develops and differentiates, three cell lineages become specified: trophectoderm (TE), epiblast, and primitive endoderm (PrE). Through two steps of cell fate decisions, 16-cell blastomeres develop into TE and an inner cell mass (ICM), and thereafter, the latter differentiates into pluripotent epiblast and PrE. Although bromodomain and extra-terminal domain (BET) proteins, such as BRD4, are necessary for the transcriptional activation of genes involved in the maintenance of mouse embryonic stem cells by occupying their enhancers, their roles in the development of mouse preimplantation are unknown.

To evaluate the effect of BET protein deficiency on cell lineage formation, we cultured preimplantation embryos in the presence of JQ1, which blocks the binding of BET bromodomains to acetylated-histones. We found BET inhibition blocked the transcriptional activation of genes, such as Nanog, Otx2, and Sox2, important for the formation of the epiblast lineage in blastocysts. Expression studies with lineage-specific markers in morulae and blastocysts revealed BET proteins were essential for the specification and maintenance of the epiblast lineage but were dispensable for the formation of primarily extraembryonic TE and PrE lineages. Additional Ingenuity Pathway Analysis and expression studies with a transcriptionally active form of signal transducer and activator of the transcription 3 (STAT3) suggested BET-dependent activation was partly associated with the STAT3-dependent pathway to maintain the epiblast lineage. To identify BET proteins involved in the formation of the epiblast lineage, we analyzed mutant embryos deficient in Brd4, Brd2, and double mutants. Abolishment of NANOG-positive epiblast cells was only evident in Brd4/Brd2 double-deficient morulae. Thus, the phenotype of JQ1-treated embryos is reproduced not by a Brd4- or Brd2-single deficiency, but only Brd4/Brd2-double deficiency, demonstrating the redundant roles of BRD2 and BRD4 in the specification of the epiblast lineage.

BET proteins are essential to the specification and maintenance of the epiblast lineage by activating lineage-specific core transcription factors during mouse preimplantation development. Among BET proteins, BRD4 plays a central role and BRD2 a complementary role in the specification and maintenance of epiblast lineages. Additionally, BET-dependent maintenance of the epiblast lineage may be partly associated with the STAT3-dependent pathway.

The online version contains supplementary material available at 10.1186/s12915-022-01251-0.

• BET
• Blastocyst
• Brd2
• Brd4
• Bromodomain
• Epiblast
• Inner cell mass
• JQ1
• Mouse
• Nanog

Metabolic rewiring and mitochondrial dynamics remodelling are hallmarks of cell reprogramming, but the roles of the reprogramming factors in these changes are not fully understood. Here we show that c-MYC induces biosynthesis of fatty acids and increases the rate of pentose phosphate pathway. Time-course profiling of fatty acids and complex lipids during cell reprogramming using lipidomics revealed a profound remodelling of the lipid content, as well as the saturation and length of their acyl chains, in a c-MYC-dependent manner. Pluripotent cells displayed abundant cardiolipins and scarce phosphatidylcholines, with a prevalence of monounsaturated acyl chains. Cells undergoing cell reprogramming showed an increase in mitochondrial membrane potential that paralleled that of mitochondrial-specific cardiolipins. We conclude that c-MYC controls the rewiring of somatic cell metabolism early in cell reprogramming by orchestrating cell proliferation, synthesis of macromolecular components and lipid remodelling, all necessary processes for a successful phenotypic transition to pluripotency.

Although advances in rapid revascularization strategies following acute myocardial infarction (AMI) have led to improved short and long-term outcomes, the associated loss of cardiomyocytes and the subsequent remodeling result in an impaired ventricular function that can lead to heart failure or death. The poor regenerative capacity of the myocardium and the current lack of effective regenerative therapies have driven stem cell research in search of a possible solution. One approach involves the delivery of stem cells to the site of injury in order to stimulate repair response. Although animal studies initially delivered promising results, the application of similar techniques in humans has been hampered by poor target site retention and oncogenic considerations. In response, several alternative strategies, including the use of non-coding RNAs (ncRNAs), have been introduced with the aim of activating and regulating stem cells or inducing stem cell status in resident cells. Circular RNAs (circRNAs) and microRNAs (miRNAs) are ncRNAs with pivotal functions in cell proliferation and differentiation, whose role in stem cell regulation and potential significance for the field of cardiac regeneration is the primary focus of this review. We also address the general advantages of ncRNAs as promising drivers of cardiac regeneration and potent stem cell regulators.

• circRNA
• differentiation
• miRNA
• stem cells

• Animals
• Cell Differentiation
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Myoblasts, Cardiac/cytology
• Myoblasts, Cardiac/metabolism
• Myoblasts, Cardiac/physiology
• RNA, Long Noncoding/genetics
• RNA, Long Noncoding/metabolism
• Regeneration

• adherens junction dynamics
• bioreactor
• fluid shear stress
• mechanopluripotency
• mouse embryonic stem cells
• vinculin
• β-catenin nuclear translocation

• ARTA
• F9 cells
• FOXC1 interactome
• HDAC2
• Nanog
• promoter analysis

The maternal-to-zygotic transition (MZT), which controls maternal signaling to synthesize zygotic gene products, promotes the preimplantation development of mouse zygotes to the two-cell stage. Our previous study reported that mouse granzyme g (Gzmg), a serine-type protease, is required for the MZT. In this study, we further identified the maternal factors that regulate the Gzmg promoter activity in the zygote to the two-cell stage of mouse embryos. A full-length Gzmg promoter from mouse genomic DNA, FL-pGzmg (−1696~+28 nt), was cloned, and four deletion constructs of this Gzmg promoter, Δ1-pGzmg (−1369~+28 nt), Δ2-pGzmg (−939~+28 nt), Δ3-pGzmg (−711~+28 nt) and Δ4-pGzmg (−417~+28 nt), were subsequently generated. Different-sized Gzmg promoters were used to perform promoter assays of mouse zygotes and two-cell stage embryos. The results showed that Δ4-pGzmg promoted the highest expression level of the enhanced green fluorescent protein (EGFP) reporter in the zygotes and two-cell embryos. The data suggested that time-specific transcription factors upregulated Gzmg by binding cis-elements in the −417~+28-nt Gzmg promoter region. According to the results of the promoter assay, the transcription factor binding sites were predicted and analyzed with the JASPAR database, and two transcription factors, signal transducer and activator of transcription 3 (STAT3) and GA-binding protein alpha (GABPα), were identified. Furthermore, STAT3 and GABPα are expressed and located in zygote pronuclei and two-cell nuclei were confirmed by immunofluorescence staining; however, only STAT3 was recruited to the mouse zygote pronuclei and two-cell nuclei injected with the Δ4-pGzmg reporter construct. These data indicated that STAT3 is a maternal transcription factor and may upregulate Gzmg to promote the MZT. Furthermore, treatment with a STAT3 inhibitor, S3I-201, caused mouse embryonic arrest at the zygote and two-cell stages. These results suggest that STAT3, a maternal protein, is a critical transcription factor and regulates Gzmg transcription activity in preimplantation mouse embryos. It plays an important role in the maternal-to-zygotic transition during early embryonic development.

• STAT3
• granzyme g
• maternal-to-zygotic transition
• preimplantation embryo

• Animals
• Blastocyst/physiology
• Cell Nucleus/genetics
• Embryonic Development/genetics
• Female
• Gene Expression Regulation, Developmental/genetics
• Granzymes/genetics
• Green Fluorescent Proteins/genetics
• Male
• Mice
• Mice, Inbred ICR
• Pregnancy
• Promoter Regions, Genetic/genetics
• STAT3 Transcription Factor/genetics
• Transcription Factors/genetics
• Transcriptional Activation/genetics
• Zygote/physiology

Abstract

Although 2,3,5,4′-Tetrahydroxystilbene-2-O-beta-glucoside (THSG) reportedly has anti-inflammatory properties, its role in inducing the dedifferentiation of human dental pulp stem cells (DPSC) into pluripotent-like stem cells remains to be determined. The purpose of this study is to evaluate the effects of THSG on the pluripotent-like possibility and mechanism of DPSC.

DPSCs were treated with THSG, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTS) assay. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of pluripotency-associated genes and oncogenes and to detect telomerase activity in the cells. Embryoid body formation assay was conducted, and pluripotency-related proteins were identified using Western blotting. Data were analyzed using one-way analysis of variance.

Cell viability, telomerase activity, and embryoid body formation were enhanced in THSG-treated DPSCs. The mRNA expression levels of pluripotent-like genes (including Nanog homeobox [NANOG], SRY-box 2 [SOX2], and POU class 5 homeobox 1 [POU5F1/OCT4]) significantly increased after THSG treatment. The expression levels of pluripotency-related genes (Janus kinase-signal transducer 2 [JAK2] and signal transducer and activator of transcription 3 [STAT3]) increased, whereas those of oncogenes (Ras, SRC, HER2, and C-sis) decreased. Furthermore, the expression levels of the phosphorylated JAK2 and STAT3 proteins significantly increased after THSG treatment.

THSG treatment may enhance the pluripotent-like possibility of DPSC through the JAK2/STAT3 axis. Hence, it may be used as an alternative cell-based therapeutic strategy in regenerative dentistry.

• 2,3,5,4′-tetrahydroxystilbene-2-O-b-glucoside
• Dental pulp stem cells
• Pluripotency

Coordinated gene expression is required for phenotypic switching between epithelial and mesenchymal phenotypes during normal development and in disease states. Trophoblast stem (TS) cells undergo epithelial-mesenchymal transition (EMT) during implantation and placentation. Mechanisms coordinating gene expression during these processes are poorly understood. We have previously demonstrated that MAP3K4-regulated chromatin modifiers CBP and HDAC6 each regulate thousands of genes during EMT in TS cells. Here we show that CBP and HDAC6 coordinate expression of only 183 genes predicted to be critical regulators of phenotypic switching. The highest-ranking co-regulated gene is the NF-κB family member Rel. Although NF-κB is primarily regulated post-transcriptionally, CBP and HDAC6 control Rel transcript levels by binding Rel regulatory regions and controlling histone acetylation. REL re-expression in mesenchymal-like TS cells induces a mesenchymal-epithelial transition. Importantly, REL forms a feedback loop, blocking HDAC6 expression and nuclear localization. Together, our work defines a developmental program coordinating phenotypic switching.

Noha Shendy et al. study the role of CBP and HDAC6 in phenotypic switching using trophoblast stem cells. They identify Rel, an NF-kB family member, to be transcriptionally coregulated by CBP and HDAC6. Surprisingly, Rel induces mesenchymal-epithelial transition and itself regulated Hdac6 expression and nuclear localization.

• Activin A
• CRISPR/Cas9
• Cytokine screen
• NANOG reporter
• Pluripotency

• Animals
• Cell Differentiation
• Cell Line
• Cell Movement
• Cytidine Diphosphate/analogs & derivatives
• Cytidine Diphosphate/metabolism
• Epithelial-Mesenchymal Transition
• Ethanolamines/metabolism
• Hepatocytes/cytology
• Hepatocytes/metabolism
• I-kappa B Kinase/metabolism
• Mice
• NF-kappa B/metabolism
• Phosphatidylethanolamine Binding Protein/metabolism
• Phosphatidylethanolamines/metabolism
• Pluripotent Stem Cells/cytology
• Pluripotent Stem Cells/metabolism
• Signal Transduction

• National Key Research and Development Program of China Stem Cell and Translational Research

• cancer stem cell
• conditioned medium
• mouse embryonic stem cells

• embryogenesis
• embryonic stem cells
• inflammatory cytokines
• innate immunity
• interferons

Acute myeloid leukemia is an aggressive disease characterized by clonal proliferation and differentiation into immature hematopoietic cells of dysfunctional myeloid precursors. Accumulating evidence shows that CD34⁺CD38^- leukemia stem cells (LSCs) are responsible for drug resistance, metastasis, and relapse of leukemia. In this study, we found that Nanog, a transcription factor in stem cells, is significantly overexpressed in CD34⁺ populations from patients with acute myeloid leukemia and in LSCs from leukemia cell lines. Our data demonstrate that the knockdown of Nanog inhibited proliferation and induced cell cycle arrest and cell apoptosis. Moreover, Nanog silencing suppressed the leukemogenesis of LSCs in mice. In addition, we found that these functions of Nanog were regulated by the insulin-like growth factor receptor (IGF1R) signaling pathway. Nanog overexpression rescued the colony formation ability of LSCs treated with picropodophyllin (PPP), an IGF1R inhibitor. By contrast, knockdown of Nanog abolished the effects of IGF2 on the colony formation ability of these LSCs. These findings suggest that the IGF2/IGF1R/Nanog signaling pathway plays a critical role in LSC proliferation.

• IGF1R
• IGF2
• Nanog
• leukemia stem cells
• proliferation

Endogenous and synthetic glucocorticoids (GCs) regulate epidermal development and combat skin inflammatory diseases. GC actions can be mediated through the GC receptor (GR) and/or the mineralocorticoid receptor (MR), highly homologous ligand-activated transcription factors. While the role of GR as a potent anti-inflammatory mediator is well known, that of MR is not as clear, nor is whether these receptors cooperate or antagonize each other in the epidermis. To address this, we generated mice with epidermal-specific loss of both receptors (double knockout, DKO), and analyzed the phenotypical and functional consequences relative to single KOs or controls (CO). At birth, DKO epidermis displayed a phenotype of defective differentiation and inflammation, which was more severe than in either single KO, featuring neutrophil-containing infiltrates, and gene dysregulation characteristic of human psoriatic lesions. This phenotype resolved spontaneously. However, in adulthood, single or combined loss of GC receptors increased susceptibility to inflammation and hyperproliferation triggered by phorbol ester which, different to CO, was not effectively counteracted by GC treatment. Also, DKOs were more susceptible to imiquimod-induced psoriasis than CO showing severe defective epidermal differentiation and microabcesses while single KOs showed an intermediate response. Immortalized DKO keratinocytes featured increased proliferation kinetics and reduced cell size, a unique phenotype relative to single KO cells. The lack of GR and MR in keratinocytes, individual or combined, caused constitutive increases in p38 and ERK activities, which were partially reversed upon reinsertion of receptors into DKO cells. DKO keratinocytes also displayed significant increases in AP-1 and NF-κB transcriptional activities, which were partially rescued by ERK and p38 inhibition, respectively. Reinsertion of GR and MR in DKO keratinocytes resulted in physical and cooperative functional interactions that restored the transcriptional response to GCs. In conclusion, our data have revealed that epidermal GR and MR act cooperatively to regulate epidermal development and counteract skin inflammation.

• Cancer stem cells
• STAT3
• Stem cells
• p63

• Animals
• Cellular Reprogramming
• Human Embryonic Stem Cells/metabolism
• Humans
• Methylation
• Mice
• MicroRNAs/metabolism
• Mouse Embryonic Stem Cells/metabolism
• Neoplasms/metabolism
• Neoplastic Stem Cells/metabolism
• Phosphorylation
• STAT3 Transcription Factor/chemistry
• STAT3 Transcription Factor/metabolism
• Transcription Factors/chemistry
• Transcription Factors/metabolism
• Tumor Suppressor Proteins/chemistry
• Tumor Suppressor Proteins/metabolism

• MEYS - NPS 1
• Grantová Agentura České Republiky
• MH CZ - DRO

Mouse embryonic stem cells (ESCs) differentiate into multiple cell types during organismal development. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from ESCs via the phosphorylation of downstream molecules such as mitogen-activated protein kinase/extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1/2 (ERK1/2). The FGF4-MEK-ERK1/2 pathway is inhibited to maintain ESCs in the undifferentiated state. However, the inhibitory mechanism of the FGF4-MEK-ERK1/2 pathway in ESCs is uncharacterized. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a post-translational modification characterized by the attachment of a single N-acetylglucosamine (GlcNAc) to the serine and threonine residues of nuclear or cytoplasmic proteins. Here, we showed that the O-GlcNAc on the phosphorylation site of PKCζ inhibits PKCζ phosphorylation (activation) and, consequently, the FGF4-PKCζ-MEK-ERK1/2 pathway in ESCs. Our results demonstrate the mechanism for the maintenance of the undifferentiated state of ESCs via the inhibition of the FGF4-PKCζ-MEK-ERK1/2 pathway by O-GlcNAcylation on PKCζ.

•

PKCζ activates the MEK-ERK1/2 pathway by FGF4 stimulation

• FGF4 signaling
• MEK-ERK1/2 pathway
• O-GlcNAc
• PKCζ
• embryonic stem cell

• Cell Differentiation/physiology
• Humans
• Neoplasms/pathology
• Neoplasms/therapy
• Neoplastic Stem Cells/pathology
• Oncologists
• Signal Transduction

• R00 CA160638 NCI NIH HHS

• Animals
• Drosophila/genetics
• Drosophila/growth & development
• Gene Regulatory Networks
• Humans
• Mammals/genetics
• Pluripotent Stem Cells/metabolism
• Retina/growth & development
• Retina/metabolism
• Transcription, Genetic

• R01 EY012549 NEI NIH HHS
• T32 HD055164 NICHD NIH HHS

• Gdap1
• cell reprogramming
• iPS cells
• mitochondrial fission
• pluripotency

• Cancer stem cells
• Gastric cancer
• Metastasis
• MicroRNA
• Stress

Bovine embryonic stem cells have potential for use in research, such as transgenic cattle generation and the study of developmental gene regulation. The Nanog may play a critical role in maintenance of the undifferentiated state of embryonic stem cells in the bovine, as in murine and human. Nevertheless, efforts to study the bovine Nanog for pluripotency-maintaining factors have been insufficient. In this study, in order to understand the mechanisms of transcriptional regulation of the bovine Nanog, the 5′-flanking region of the Nanog was isolated from ear cells of Hanwoo. Results of transient transfection using a luciferase reporter gene under the control of serially deleted 5′-flanking sequences revealed that the −134 to −19 region contained the positive regulatory sequences for the transcription of the bovine Nanog. Results from mutagenesis studies demonstrated that the Sp1-binding site that is located in the proximal promoter region plays an important role in transcriptional activity of the bovine Nanog promoter. The electrophoretic mobility shift assay with the Sp1 specific antibody confirmed the specific binding of Sp1 transcription factor to this site. In addition, significant inhibition of Nanog promoter activity by the Sp1 mutant was observed in murine embryonic stem cells. Furthermore, chromatin-immunoprecipitation assay with the Sp1 specific antibody confirmed the specific binding of Sp1 transcription factor to this site. These results suggest that Sp1 is an essential regulatory factor for bovine Nanog transcriptional activity.

• Bovine
• Embryonic Stem Cells
• Nanog
• Sp1
• Transcription Factors

• Animals
• Cell Line
• Cellular Reprogramming
• Dynamins/genetics
• Dynamins/metabolism
• Dynamins/physiology
• Induced Pluripotent Stem Cells/cytology
• Induced Pluripotent Stem Cells/metabolism
• Induced Pluripotent Stem Cells/ultrastructure
• Kruppel-Like Factor 4
• Kruppel-Like Transcription Factors/genetics
• Kruppel-Like Transcription Factors/metabolism
• MAP Kinase Signaling System
• Mice
• Mitochondria/metabolism
• Mitochondria/ultrastructure
• Mitochondrial Dynamics
• Octamer Transcription Factor-3/genetics
• Octamer Transcription Factor-3/metabolism
• Phosphorylation
• Proto-Oncogene Proteins c-myc/genetics
• Proto-Oncogene Proteins c-myc/metabolism
• SOXB1 Transcription Factors/genetics
• SOXB1 Transcription Factors/metabolism

Embryonic stem cell-derived mesenchymal stromal cells (MSCs; also known as mesenchymal stem cells) represent a promising source for bone regenerative medicine. Despite remarkable advances in stem cell biology, the molecular mechanism regulating differentiation of human embryonic stem cells (hESCs) into MSCs remains poorly understood. Here, we report that inhibition of IκB kinase (IKK)/nuclear factor kappa B (NF-κB) signaling enhances differentiation of hESCs into MSCs by expediting the loss of pluripotent markers and increasing the expression of MSC surface markers. In addition, a significantly higher quantity of MSCs was produced from hESCs with IKK/NF-κB suppression. These isolated MSCs displayed evident multipotency with capacity to terminally differentiate into osteoblasts, chondrocytes, and adipocytes in vitro and to form bone in vivo. Collectively, our data provide important insights into the role of NF-κB in mesenchymal lineage specification during hESC differentiation, suggesting that IKK inhibitors could be utilized as an adjuvant in generating MSCs for cell-mediated therapies.

•

NF-κB signaling inhibits differentiation of hESCs

• IKK
• MSCs
• NF-κB
• embryonic stem cells
• mesoderm

• HCC
• HCV
• NASH
• Obesity

• GLI proteins
• Hedgehog signaling pathway
• Nanog
• differentiation
• embryonic stem cell
• repressor
• stem cells
• transcription repressor

• HCC
• NANOG
• OXPHOS
• fatty acid
• liver
• metabolic reprogramming
• self-renewal
• tumor-initiating stem-like cells (TICs)

• cell differentiation
• cell division
• embryonic stem cell
• gene transcription
• promoter

• cancer stem cells
• chemotherapy
• radiotherapy
• signaling pathways

• Animals
• Breast Neoplasms/pathology
• Breast Neoplasms/therapy
• Female
• Humans
• Neoplasm Recurrence, Local/pathology
• Neoplastic Stem Cells/drug effects
• Neoplastic Stem Cells/pathology
• Neoplastic Stem Cells/radiation effects
• Signal Transduction

• P30 CA125123 NCI NIH HHS
• R01 CA127857 NCI NIH HHS
• U54 CA149196 NCI NIH HHS
• P30-CA125123 NCI NIH HHS

• Cancer stem cells
• Cell signaling
• Drug target
• Experimental models
• Fluorescence activated cell sorting
• Fluorescent protein reporter genes
• Lentiviral vector
• Signal transducer and activator of transcription