Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pluripotent stem cells derived from preimplantation embryos, primordial germ cells or teratocarcinomas are currently unique in undergoing prolonged symmetrical self-renewal in culture. For mouse embryonic stem (ES) cells, self-renewal is dependent on signals from the cytokine leukaemia inhibitory factor (LIF) and from either serum or bone morphogenetic proteins (BMPs). In addition to the extrinsic regulation of gene expression, intrinsic transcriptional determinants are also required for maintenance of the undifferentiated state. These include Oct4, a member of the POU family of homeodomain proteins and a second recently identified homeodomain protein, Nanog. When overexpressed, Nanog allows ES cells to self-renew in the absence of the otherwise obligatory LIF and BMP signals. Although Nanog can act independent of the LIF signal, a contribution of both pathways provides maximal self-renewal efficiency. Nanog function also requires Oct4. Here, we review recent progress in ES cell self-renewal, relate this to the biology of teratocarcinomas and offer testable hypotheses to expose the mechanics of ES cell self-renewal.
 ...
PMID:Self-renewal of teratocarcinoma and embryonic stem cells. 1537 75

Apatites play a crucial role in the body and have been used extensively in biomedical implants. The influence on stem cell behaviour is not known and so this study will explore whether sintered carbonated apatites are favourable for propagation of stem cells. Different weight substitutions of carbonated apatite, specifically 2.5 wt% (2.5 wt%CAP) and 5 wt% (5 wt%CAP), were sintered and characterised prior to the investigation of their potential as a matrix for the support of mouse embryonic stem (ES) cells. Characterisation of the apatites included elemental analysis, X-ray diffraction, surface roughness, specific surface area, density, and solubility. The ability of carbonated apatite to support mouse ES cell colonisation and maintenance in the presence of leukaemia inhibitory factor was determined by an enumeration of live versus dead cells within a population, and immunoreactivity to Oct4, a transcription factor and stem cell marker, following growth on each matrix. It was found that while both compositions allowed for the colonisation of mouse ES cells, the cells were not maintained in an undifferentiated state, as evidenced by a reduction in the number of cells staining positive for Oct4 expression. This study shows that an increase in carbonate content within sintered apatites leads to a higher cell number, a desired aspect for stem cells to populate scaffolds intended for tissue engineering. This study presents carbonated apatites as a suitable matrix for the initial colonisation and differentiation of ES cells for tissue engineering applications.
 ...
PMID:Mouse embryonic stem cell colonisation of carbonated apatite surfaces. 1609 98

Intrinsic regulators of the pluripotency of mouse ES (embryonic stem) cells include the homeodomain proteins Oct4 and the recently identified Nanog. When overexpressed, Nanog displays the unique attribute of robustly sustaining ES cell self-renewal in the absence of the otherwise requisite extracellular stimulation by LIF (leukaemia inhibitory factor) and BMP (bone morphogenetic protein). Here, we review our current understanding of the function of Nanog in pluripotent stem cells both in vitro and in vivo.
 ...
PMID:The homeodomain protein Nanog and pluripotency in mouse embryonic stem cells. 1624 59

The reciprocal chromosomal translocation t(4;11) is correlated with infant, childhood, adult and therapy-related high-risk acute leukemia. Here, we investigated the biological effects of MLL.AF4, AF4.MLL or the combination of both reciprocal fusion proteins in a conditional in vitro cell culture model system. Several parameters like cell growth, cell cycling capacity, apoptotic behavior and growth transformation were investigated under physiological and stress conditions. Co-transfected cells displayed the highest resistance against apoptotic triggers, cell cycling capacity and loss-of-contact inhibition. These analyses were complemented by gene expression profiling experiments and specific gene signatures were established for each of the three cell lines. Interestingly, co-transfected cells strongly upregulate the homeobox gene Nanog. In combination with Oct4, the Nanog homeoprotein is steering maintenance of pluripotency and self-renewal in embryonic stem cells. Transcription of Nanog and other stem cell factors, like Oct4 and Bmi1, was verified in biopsy material of t(4;11) patient cells which express both reciprocal t(4;11) fusion genes. In conclusion, the presence of both reciprocal MLL fusion proteins confers biological properties known from t(4;11) leukemia, suggesting that each of the two fusion proteins contribute specific properties and, in combination, also synergistic effects to the leukemic phenotype.
 ...
PMID:Combined effects of the two reciprocal t(4;11) fusion proteins MLL.AF4 and AF4.MLL confer resistance to apoptosis, cell cycling capacity and growth transformation. 1713 Aug 30

Induced pluripotent stem (iPS) cells are generated from somatic cells by genetic manipulation. Reprogramming entails multiple transgene integrations and occurs apparently stochastically in rare cells over many days. Tissue stem cells may be subject to less-stringent epigenetic restrictions than other cells and might therefore be more amenable to deprogramming. We report that brain-derived neural stem (NS) cells acquire undifferentiated morphology rapidly and at high frequency after a single round of transduction with reprogramming factors. However, critical attributes of true pluripotency--including stable expression of endogenous Oct4 and Nanog, epigenetic erasure of X chromosome silencing in female cells, and ability to colonise chimaeras--were not attained. We therefore applied molecularly defined conditions for the derivation and propagation of authentic pluripotent stem cells from embryos. We combined dual inhibition (2i) of mitogen-activated protein kinase signalling and glycogen synthase kinase-3 (GSK3) with the self-renewal cytokine leukaemia inhibitory factor (LIF). The 2i/LIF condition induced stable up-regulation of Oct4 and Nanog, reactivation of the X chromosome, transgene silencing, and competence for somatic and germline chimaerism. Using 2i /LIF, NS cell reprogramming required only 1-2 integrations of each transgene. Furthermore, transduction with Sox2 and c-Myc is dispensable, and Oct4 and Klf4 are sufficient to convert NS cells into chimaera-forming iPS cells. These findings demonstrate that somatic cell state influences requirements for reprogramming and delineate two phases in the process. The ability to capture pre-pluripotent cells that can advance to ground state pluripotency simply and with high efficiency opens a door to molecular dissection of this remarkable phenomenon.
 ...
PMID:Promotion of reprogramming to ground state pluripotency by signal inhibition. 2007 93

The genetic program of embryonic stem (ES) cells is orchestrated by a core of transcription factors that has OCT4, SOX2, and NANOG as master regulators. Protein levels of these core factors are tightly controlled by autoregulatory and feed-forward transcriptional mechanisms in order to prevent early differentiation. Recent studies have shown that knockdown of Esrrb (estrogen-related-receptor beta), a member of the nuclear orphan receptor family, induces differentiation of mouse ES cells cultured in the presence of leukemia inhibitory factor. It was however not known how knocking down Esrrb exerts this effect. Herein we have identified two ESRRB binding sites in the proximal 5'-untranslated region of the mouse Oct4 gene, one of which is in close proximity to a NANOG binding site. Both ESRRB and NANOG are necessary for maintaining the activity of this promoter in ES cell lines. We have also demonstrated that the two transcription factors interact through their DNA binding domains. This interaction reciprocally modulates their transcriptional activities and may be important to fine-tune ES cell pluripotency. Supporting all of these data, stable transfection of Esrrb in ES cell lines proved sufficient to sustain their characteristics in the absence of leukemia-inhibitory factor. In summary, our experiments help to understand how Esrrb coordinates with Nanog and Oct4 to activate the internal machinery of ES cells.
 ...
PMID:Esrrb activates Oct4 transcription and sustains self-renewal and pluripotency in embryonic stem cells. 1895 14

In the present study, buffalo embryonic stem-like (ES-like) cell lines were successfully isolated, cultured and characterized. From a total of 92 normal buffalo embryos obtained by in vitro fertilization, 18 were morulae, 33 were blastocyst and 41 were hatched blastocyst, the inside of morulae or inner cell masses of blastocysts were isolated mechanically and cultured onto mitomocin-C-inactivated buffalo embryonic fibroblasts as feeder layers. Alkaline phosphatase (AP) of ES-like cells, as well as the specific stage embryonic antigen SSEA-1, SSEA-3, SSEA-4 and transcription factor OCT-4, was used to evaluate the characterization of the cells. The spontaneous differentiation of ES-like cells was induced by culturing on leukaemia inhibitory factor-free medium for more than 2 weeks without passage. To evaluate mark gene expression, total RNA was extracted from cells, and specific primers were used for reverse transcriptase-polymerase chain reaction (RT-PCR). After 8-10 days of culture, primary ES-like cell colonies were formed in 0% (0/18) of morulae, 24.24% (8/33) of blastocysts and 60.98% (25/41) of hatched blastocysts, respectively. The forming rate of primary ES-like cells colonies in hatched blastocyst group was significantly (p < 0.05) higher than the obtained for other groups. Two ES-like cell lines could survive to eight passages at least by using the method of mechanical dissociation, but just three passages by using the method of enzymatic dissociation. The cells formed large, multicellular colonies with distinct boundaries, exhibited many important features of ES/ES-like cells, including positive AP, SSEA-1, SSEA-3 and SSEA-4 activity. Undifferentiated buffalo ES-like cells expressed Oct-4, Nanog, Sox2 gene mRNA. In vitro differentiation experiments had demonstrated that those cells were pluripotent.
 ...
PMID:Generation and characterization of embryonic stem-like cell lines derived from in vitro fertilization Buffalo (Bubalus bubalis) embryos. 1914 15

Recently, we identified in adult tissues a population of Oct4(+)SSEA-1(+)Sca-1(+)lin(-)CD45(-) very small embryonic-like stem cells (VSELs). First, to address recent controversies on Oct4 expression in cells isolated from adult organs, we show here evidence that Oct4 promoter in bone marrow (BM)-derived VSELs has an open chromatin structure and is actively transcribed. Next, to explain VSELs quiescence and lack of teratoma formation, we demonstrate a unique DNA methylation pattern at some developmentally crucial imprinted genes, showing hypomethylation/erasure of imprints in paternally methylated and hypermethylation of imprints in maternally methylated ones. These epigenetic characteristics leading to upregulation in VSELs of H19 and p57(KIP2) (also known as Cdkn1c) and repression of Igf2 and Rasgrf1 explain VSEL's quiescent status. Interestingly, this unique pattern in imprinted gene methylation is reverted in cocultures with a C2C12 supportive cell-line when VSELs are induced to form VSEL-derived spheres (VSEL-DSs) enriched for stem cells able to differentiate into all three germ layers. Therefore, we suggest that the proliferative/developmental potential of Oct4(+) VSELs is epigenetically regulated by expression of Oct4 and some imprinted genes, and postulate that restoring the proper methylation pattern of imprinted genes will be a crucial step for using these cells in regenerative medicine.
Leukemia 2009 Nov
PMID:Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived Oct4(+) very small embryonic-like stem cells. 1964 21

Mouse embryonic stem (ES) cells are conventionally cultured with Leukemia Inhibitory Factor (LIF) to maintain self-renewal.(1) However, LIF is expensive and activation of the LIF/JAK/STAT3 pathway is not absolutely required to maintain the self-renewal state.(2) The SC1 small molecule may be an economical alternative to LIF. SC1 functions through dual inhibition of Ras-GAP and ERK1.(3) Illustration of its mechanism of action makes it a useful tool to study the fundamental molecular mechanism of self-renewal. Here we demonstrate the procedure for culturing mouse ES cells in the presence of SC1 and show that they are able to maintain self-renewal in the absence of LIF. Cells cultured with SC1 showed similar morphology compared to cells maintained with LIF. Both exhibited typical mouse ES morphology after five passages. Expression of typical pluripotency markers (Oct4, Sox2, Nanog, and SSEA1) was observed after five passages in the presence of SC1. Furthermore, SC1 caused no overt toxicity on mouse ES cells.
 ...
PMID:The use of SC1 (Pluripotin) to support mESC self-renewal in the absence of LIF. 1992 98

The objective of this study was to investigate the capability of bank vole (Myodes glareolus) embryonic cells to sustain their pluripotent character during in vitro culture, and to determine the optimal conditions for derivation of embryonic stem (ES) cells. We compared the presence of specific pluripotency (Oct4, Ssea1) and differentiation markers (Gata4 - primitive endoderm marker; Cdx2 - trophectoderm marker) in blastocysts and inner cell mass (ICM) outgrowths obtained from blastocysts of bank vole, and two mouse hybrids F1(C57Bl/6xCBA/H) and F1(C57Bl/6x129/Sv), which differ in the permissiveness of giving rise to ES cells. We found that, in contrast to mouse, the expression of pluripotency markers in the cells of bank vole ICM outgrowths is progressively downregulated and rapidly lost by the 4th day of culture. This correlates with the appearance of cells expressing Gata4 and Cdx2, indicating differentiation towards primitive endoderm and derivatives of trophectoderm, respectively. We have also shown that heterologous cytokine leukaemia inhibitory factor (LIF) in conjunction with either homologous or heterologous feeder layer is unable to delay differentiation and preserve pluripotency of bank vole embryonic cells. Thus, the conditions optimised for mouse do not support the maintenance of bank vole embryonic cells in the undifferentiated state and do not allow for the isolation of the ES cells. Instead, combination of fibroblast growth factor 2 and activin A allows retention of Oct4 expression in bank vole blastocyst outgrowths during 4-day culture, indicating that signaling pathways operating in human, rather than mouse ES cells, might be involved in the process of self-renewal of bank vole embryonic cells.
 ...
PMID:Pluripotency of bank vole embryonic cells depends on FGF2 and activin A signaling pathways. 2001 53


1 2 3 4 5 Next >>