Abstract P001: HDAC1 Plays an Important Role in the Differentiation of Embryonic Stem Cells and Induced Pluripotent Stem Cells into Cardiovascular Lineages

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Eneda Hoxha ◽  
Erin Lambers ◽  
Veronica Ramirez ◽  
Prasanna Krishnamurthy ◽  
Suresh Verma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Full Potential ◽  
Early Differentiation ◽  
Increased Risk ◽  
Mes Cells

Despite advancements in the treatment of myocardial infarction (MI), the majority of patients are at increased risk for developing heart failure due to the loss of cardiomyocytes and microvasculature. Some of the main obstacles in the realization of the full potential of iPS/ES cells arise from incomplete and poorly understood molecular mechanisms and epigenetic modifications that govern their pluripotency and directed differentiation. Real-time array experiments revealed that HDAC1 is highly expressed in pluripotent cells. Additionally the lack of this molecule is embryonic lethal, suggesting it plays a key role in development. Thus, we hypothesized that HDAC1 plays a critical role in directing cardiovascular differentiation of mES and iPS cells in vitro. HDAC1 was knocked down in mES cells (C57BL/6) and iPS cells using a shRNA vector. Differentiation through embryoid body (EB) was induced in wild type mES cells and iPS cells and in their HDAC1-null counterparts and the ability of these cells to differentiate into three early embryonic lineages and more specifically cardiovascular lineage was monitored. EBs lacking HDAC1 differentiated slower and showed delayed suppression of pluripotent genes such as Oct4 and Sox2. ChiP experiments revealed high histone acetylation levels at the promoter regions of these genes during early differentiation. In addition cells lacking HDAC1 showed reduced expression of early markers for all three germ layers. HDAC1-null EBs also showed delayed and reduced spontaneous beating. Expression of cardiomyocite markers as well as markers of other cardiovascular lineages was repressed in HDAC1 -null cells. However, supplementation with BMP2 during early differentiation recovered the ability in the HDAC1-null cells to differentiate into endodermal and mesodermal lineages, but not ectodermal. We propose that HDAC1 plays a critical role in early development and cardiovascular differentiation of mES and iPS cells by repressing pluripotent genes and allowing for expression of early developmental genes such as SOX17 and BMP2. Further research in the molecular mechanisms involved in this process will greatly aid our understanding of the epigenetic circuitry of pluripotency and differentiation in ES and iPS cells.

Abstract 340: From Stem Cells to Cardiomyocytes: HDAC1 Induces Cardiovascular Differentiation by Regulating SOX17-BMP2 Expression in Early Development.

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Eneda Hoxha ◽  
Erin Lambers ◽  
Veronica Ramirez ◽  
Prasanna Krishnamurthy ◽  
Suresh Verma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Ips Cells ◽  
Full Potential ◽  
Pluripotent Cells ◽  
Differentiation Potential ◽  
Histone Deacetylase 1 ◽  
Specific Differentiation ◽  
Induced Pluripotent

Cardiomyocytes derived from embryonic and induced pluripotent stem cells (ES/iPS) provide an excellent source for cell replacement therapies following myocardial ischemia. However, some of the obstacles in the realization of the full potential of iPS/ES cells arise from incomplete and poorly understood molecular mechanisms and epigenetic modifications that govern their cardiovascular specific differentiation. We identified Histone Deacetylase 1 (HDAC1) as a crucial regulator in early differentiation of mES and iPS cells. We propose a novel pathway in which HDAC1 regulates cardiovascular differentiation by regulating SOX17 which in turn regulates BMP2 signaling in differentiating pluripotent cells. Utilizing stable HDAC1 knock-down (HDAC1-KD) cell lines, we report an essential role for HDAC1 in deacetylating regulatory regions of pluripotency-associated genes during early cardiovascular differentiation. HDAC1-KD cells show severely repressed cardiomyocyte differentiation potential. We propose a novel HDAC1-BMP2-SOX17 dependent pathway through which deacetylation of pluripotency associated genes leads to their suppression and allows for early cardiovascular-associated genes to be expressed and differentiation to occur. Furthermore, we show that HDAC1 affects DNA methylation both during pluripotency and differentiation and plays a crucial, non-redundant role in cardiovascular specific differentiation and cardiomyocyte maturation. Our data elucidates important differences between ES and iPS HDAC1-KD cells that affect their ability to differentiate into cardiovascular lineages. As varying levels of chromatin modifying enzymes are likely to exist in patient derived iPS cells, understanding the molecular circuitry of these enzymes in ES and iPS cells is critical for their potential therapeutic applications in regenerative medicine. Further research in the molecular mechanisms involved in this process will greatly aid our understanding of the epigenetic circuitry of pluripotency and differentiation in pluripotent cells.

199 DIFFERENTIATION OF HIGHLY ENRICHED OLIGODENDROCYTE PRECURSORS AND MATURE OLIGODENDROCYTES FROM RHESUS MONKEY EMBRYONIC STEM CELLS

2006 ◽  
Vol 18 (2) ◽  
pp. 207
Author(s):  
T. Li ◽  
Y. Xie ◽  
W. Ji
Keyword(s):  
Stem Cells ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Rhesus Monkey ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Embryonic Stem ◽  
Oligodendrocyte Differentiation ◽  
Culture Systems ◽  
Oligodendrocyte Precursors

Generating homologous oligodendrocytes are required for studying the molecular mechanisms of oligodendrogliogenesis and for providing donor cells for transplantation therapies. Previous studies have shown that embryonic stem (ES) cells can be induced to generate neural stem cells with many kinds of culture systems; however, few or no oligodendrocytes were obtained from these culture systems. Here we present a simple method containing five steps for obtaining highly enriched oligodendrocyte precursors (75 � 6.8%) and mature oligodendrocytes (81 � 8.6%) from rhesus monkey embryonic stem (rES) cells. We expanded rES cells on a feeder layer of irradiated MESF (ear skin fibroblasts from a one-week-old rhesus monkey), formed embryoid bodies (EBs), promoted Day 9 (3 days in hanging drop and 6 days in suspension) differentiation into highly enriched (90.2 � 6.1%) neural progenitors (NPs) with hepatocyte growth factor (HGF) and G5 supplement [containing 5 ng/mL (bFGF) and 10 ng/mL epidermal growth factor (EGF)], purified NPs with 0.0625% trypsin in 0.04% EDTA (98% of cells were nestin-positive), amplified those progenitors in HGF and G5 media for two months, and then induced oligodendrocyte precursors differentiation in the absence of G5, but in the presence of 20 ng/mL HGF for 2 days. To obtain terminal oligodendrocytes, neurospheres cultured for 2 months were plated on laminin-coated plates for 3 weeks in the presence of HGF. The results showed that differentiated cells expressed myelin basic protein (MBP) and had typical mature oligodendrocyte morphology. Our studies also revealed that HGF significantly increased the NP proliferation speed (P < 0.05) by both decreasing cell apoptosis rate (P < 0.05) and shortening cell cycle time (P < 0.05) in the presence of G5. Additionally, HGF promoted oligodendrocyte maturation by increasing the length and number of branches and the expression of MBP. To test whether the original HGF had similar functions for oligodendrocyte specification, a series of experiments were evaluated by adding HGF or G5 to differentiation or expansion media at different differentiation stages. The results demonstrated that the ability of HGF responsiveness to initiate oligodendrocyte differentiation was regulated by G5 and by HGF alone without G5-induced rES cell differentiation into neurons. Further studies showed that the crucial time point of G5 action was from EBs to NPs; the early addition of HGF to EBs in the presence of G5 increased oligodendrocyte differentiation rate, but was not necessary, and the treatment during the first 2 days was enough to produce a similar effect; and HGF was required for terminal oligodendrocyte differentiation from NPs. Taken together, these results showed that HGF and G5 cooperatively promote rES cell differentiation into highly enriched oligodendrocyte precursors and mature oligodendrocytes.These observations set the method for obtaining highly enriched oligodendrocytes from ES cells in the nonhuman primate for clinical application and provide a platform to probe the molecular mechanisms that control oligodendrocyte differentiation.

BMP4 and TGFbeta Differentially Regulate CD34+ Progenitor Development in Human Embryonic Stem Cells through SMAD-Dependent Pathway

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 889-889
Author(s):  
ZacK Z. Wang ◽  
Hao Bai ◽  
Melanie Arzigian ◽  
Yong-Xing Gao ◽  
Wen-Shu Wu
Keyword(s):  
Stem Cells ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Progenitor Cells ◽  
Embryoid Body ◽  
Es Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Bmp Signaling ◽  
Cd34 Cells

Abstract Pluripotent stem cells derived from patients, including embryonic stem (ES) cells and “induced pluripotent stem” (iPS) cells, are a promising area of regenerative medical research. A major roadblock toward human clinical therapies using ES cells or iPS cells is to define the factors that direct ES cell differentiation into lineage specific cells. We previously established a simple and efficient human embryonic stem cell (hESC) differentiation system to generate CD34+/CD31+ progenitor cells that gave rise to hematopoietic and endothelial cells (Nat Biotech.25:317, 2007). To advance potential clinical application and to define the effects of growth factors on hematopoietic and vascular differentiation, we assessed hESC differentiation on human feeder cells in serum-free condition without intermediate embryoid body (EB) formation. We investigated the roles of BMPs, TGFbeta, VEGF, and FGF2 in directing hESC differentiation. Growth factors were added into culture at different time points to test their stage specific roles. Our study demonstrated that BMP proteins, including BMP2, BMP4, and BMP7, but not BMP9, had synergic effects to VEGF and FGF-2 on hESC differentiation to CD34+/CD31+ progenitor cells. BMP4 was essential to initial CD34+/CD31+ cell development, whereas VEGF and FGF2 promoted the differentiation in later stage, suggesting the sequential roles of BMP4, VEGF and FGF2 in directing hESC differentiation to CD34+/CD31+ progenitor cells. TGFbeta or activin promoted hESC differentiation into CD34+/CD31− cells that were unable to give rise to hematopoietic, endothelial, and smooth muscle cells. Furthermore, TGFbeta or activin activated Smad2/3 signaling, and suppressed BMP4-induced CD34+/CD31+ cells. Microarray analysis revealed that BMP4-induced CD34+ cells expressed hematopoietic, endothelial and smooth muscle genes, including GATA2, gamma globins, VE-Cad, KDR, CD31, Tie2, and aortic smooth muscle actin, whereas TGFbeta-induced CD34+ cells expressed pluripotent markers and endoderm markers, including Oct3/4, Sox2, and Nanog, HHEX, GATA6, and FoxA2. Both canonical BMP signaling (Smad1/5/8-dependent) and non-canonical BMP signaling (p38 MAPK and p42 ERK pathway) were activated by BMP4 in hESCs. Dorsomorphin specifically inhibited BMP4-mediated phosphorylation of Smad1/5/8, and blocked hESC differentiation into CD34+/CD31+ cells. In summary, BMPs and TGFbeta regulate distinct populations of CD34+ cells in hESCs. BMP-Smad1/5/8 pathway is critical for hematopoietic and vascular progenitor development.

305 TRANSPOSON-MEDIATED REPROGRAMMING OF LIVESTOCK SOMATIC CELLS TO INDUCED PLURIPOTENT STEM CELLS

2013 ◽  
Vol 25 (1) ◽  
pp. 300
Author(s):  
T. R. Talluri ◽  
D. Hermann ◽  
B. Barg-Kues ◽  
K. Debowski ◽  
R. Behr ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Insertional Mutagenesis ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Sleeping Beauty ◽  
Major Step ◽  
Increased Risk ◽  
Induced Pluripotent

The elusive nature of embryonic stem cells in livestock makes reprogramming of somatic cells to induced pluripotent stem (iPS) cells a promising approach for targeted genetic modifications. The first attempts to produce iPS cells from livestock species were made using retro- and lentiviral vectors, which are associated with an increased risk of insertional mutagenesis and which are not easily removable after reprogramming. Here, we describe a nonviral method for the derivation of porcine and bovine iPS cells, using Sleeping Beauty (SB) and piggyBac (PB) transposon systems. The transposons encode the murine or primate reprogramming factors OCT4, SOX2, KLF4, MYC, and LIN28, separated by self-cleaving peptide sequences, respectively. In addition, the PB transposon cassette contains a NANOG-cDNA. The SB or PB transposon-reprogrammed porcine iPS cells expressed typical markers of embryonic stem cells (SSEA1, SSEA4, TRA-1-60, and endogenous stemness genes), showed long-term proliferation under feeder-free culture conditions, differentiated into cell types of the 3 germ layers in vitro, and formed teratomas after subcutaneous injection into immune-deficient nude mice. Both transposon systems are currently being tested in bovine fibroblasts. The results are a major step towards the derivation of authentic porcine and bovine iPS cells, in which the transposon transgenes can be eliminated after reprogramming.

HoxA11 Is Expressed in the Developing Hemangioblast as Well as Early Hematopoietic Precursor Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4206-4206
Author(s):  
Regina D. Horvat-Switzer ◽  
Alexis A. Thompson
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mrna Expression ◽  
Progenitor Cells ◽  
Hox Genes ◽  
Es Cells ◽  
Critical Role ◽  
Embryonic Stem ◽  
Rt Pcr ◽  
Hematopoietic Precursor

Abstract Congenital amegakaryocytic thrombocytopenia with radio-ulnar synostosis is associated with mutations in the HOXA11 gene, suggesting that HoxA11 may play a role in megakaryocytic lineage commitment or differentiation. The HOX genes encode transcription factors that are involved in cellular differentiation in embryonic as well as adult tissues. Numerous studies have identified HOX genes as important regulators of various aspects of hematopoiesis including self-renewal, proliferation, differentiation and leukemogenesis. Our initial studies failed to identify the expression of HoxA11 in platelets, TPO-induced CD34+ umbilical cord stem cells or normal bone marrow. More recently our lab has detected a small amount of HoxA11 mRNA in cells isolated from unfractionated human cord blood, suggesting the expression of HoxA11 may occur in a small subset of early hematopoietic or stromal cells. To test this hypothesis we have employed a murine embryonic stem (ES) cell culture system. Co-culture of ES cells and the bone marrow stromal cell line, OP9, can give rise to primitive as well as definitive hematopoietic progenitors in the absence of leukemia inhibitory factor (LIF). By day 6, ES cells on OP9 can differentiate into mesodermal colonies, which contain a bi-potential progenitor known as the hemangioblast. The hemangioblast can further differentiate into either a hematopoietic or endothelial lineage. To determine when HoxA11 is expressed we have employed this model using green fluorescent protein (GFP) expressing ES cells grown on OP9 and differentiated into hematopoietic precursors in the absence of LIF. Nested RT-PCR revealed that HoxA11 mRNA is highly expressed in ES cells following 6 days (D6) on OP9. HoxA11 expression was restricted to D6 ES cells, as HoxA11 mRNA was not found in OP9 cells alone or ES cells differentiated on OP9 for 0, 3, or 9 days. RT-PCR revealed HoxA11 mRNA expression coincided with the expression of flk-1, a marker for the hemangioblast. Since HoxA11 expression is concurrent with hemangioblast differentiation, we sought to determine if the hemangioblast is the cell that expressed HoxA11. Using flow cytometery and fluorescence activated cell sorting (FACS) analysis we separated D6 ES cells into flk-1 positive (flk-1+) and negative (flk-1−) populations and investigated which population expressed HoxA11. Nested RT-PCR revealed that HoxA11 mRNA expression is found in both the flk-1+ and flk-1- fractions. We further analyzed these fractions by RT-PCR for SCL/Tal-1. SCL/Tal-1 is a transcription factor that plays a critical role in the commitment of mesoderm into hematopoietic progenitor cells. We find SCL/Tal-1 mRNA also expressed in both flk-1+ and flk-1- fractions, which parallels HoxA11 mRNA expression. These data suggest HoxA11 expression occurs in the flk-1+ hemangioblast but also possibly in a flk-1-/SCL+ hematopoietic precursor cell population. Current studies are underway to determine the cell fate and role of the HoxA11 expressing progenitor cell. Taken together, these data are the first findings of HoxA11 expression in early progenitor cells as well as the first evidence of controlled HoxA11 regulation during early hematopoietic development.

Expression of Functional Toll-Like Receptor 2 on Mouse Embryonic Stem Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4746-4746
Author(s):  
Tammi Taylor ◽  
Wilbert Derbigny ◽  
Young-June Kim ◽  
Hal E. Broxmeyer
Keyword(s):  
Stem Cells ◽  
Cell Lines ◽  
Nuclear Translocation ◽  
Es Cells ◽  
Mrna Level ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Toll Like Receptor ◽  
Undifferentiated State ◽  
Mes Cells

Abstract Embryonic stem (ES) cells have the capacity to produce all cell types of the body. Understanding murine ES (mES) cell proliferation, survival, differentiation, and self renewal will enhance knowledge of developmental biology and essential use of ES cells. Recently, Toll Like Receptor (TLR) activation has been shown by others to play a role in influencing the differentiation of hematopoietic stem cells. Previous studies have also shown that TLR activation prevents mesenchymal stem cell differentiation into adipocytes, chondrocytes, and osteocytes and plays a role in bone repair. We hypothesized that certain TLR’s would be expressed on mES cells and that the ligands for these expressed TLR’s would induce functional activity in the mESC’s. Therefore, we wanted to determine if TLRs are expressed on mES cells and if so, are they functional. Three different mES cell lines (R1, CGR8, and E14) were used to determine if TLRs are expressed at the mRNA level using primers for murine TLR1-9 mRNA. We found that TLR’s 1, 2, 3, 6, and 9 were expressed at the mRNA level, but TLR’s 4, 5, 7, and 8 were not. Based on the availability of antibodies to TLR’s, and using flow cytometry, we found expression of TLR2 but not TLR 4 on the surface of all three mES cell lines. TLR ligands were used to treat mES cells in the presence of leukemia inhibitory factor (LIF) for an hour. Activation of TLR2 by its ligand Pam3Cys, a synthetic tri-acyl lipoprotein, on mES cells induced NF-κβ nuclear translocation when compared to ES cells not stimulated with TLR ligands. LPS, the ligand for TLR4 did not induce NF-κβ nuclear translocation on ES cells, consistent with lack of cell surface expression of TLR4 on mES cells. TLR expression and TLR ligand interaction were not associated with changes in the morphology of the mES cells or expression of Oct-4, SSEA-1, KLF-4, or Sox-2, markers for maintenance of the undifferentiated state of mES cells. This suggests that the cells remain in an undifferentiated state even after TLR activation by Pam3Cys in the presence of LIF. Thus our study has identified functionally active TLR2 on the surface of mES cells, information that may be of use to further defining a role for TLR’s on ES cells, and for manipulation of other ES cell functions.

Patient-Specific Pluripotent Stem Cells for Hematologic Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. SCI-40-SCI-40
Author(s):  
George Q. Daley
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Nuclear Transfer ◽  
Es Cells ◽  
Somatic Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Patient Specific ◽  
Direct Reprogramming ◽  
Disease Specific

Abstract Abstract SCI-40 Pluripotent stem cells can be isolated from embryos (embryonic stem cells; ES cells) or generated by direct reprogramming of somatic cells (induced pluripotent stem cells; iPS cells). Both types can be differentiated into a multitude of cell lineages to serve disease research and cell replacement therapies. Additionally, genetically matched pluripotent stem cells generated via nuclear transfer (ntES cells), parthenogenesis (pES cells), or direct reprogramming (iPS cells) are a possible source of histocompatible cells and tissues for transplantation. We have used customized ntES cells to repair genetic immunodeficiency in mice (Rideout et al., Cell 2002); however, generation of ES cells by nuclear transfer remains inefficient, and to date has not been achieved with human cells. We have also generated ES cells with defined histocompatibility loci by direct parthenogenetic activation of the unfertilized oocyte (Kim et al., Science 2007). Compared to ES cell lines from fertilized embryos, pES cells display comparable in vitro hematopoietic activity, but appear compromised in repopulating hematopoiesis in irradiated adult mouse recipients. We are currently comparing the performance of ntES, pES, and iPS cells in murine models of thalassemia. We have generated human iPS cells by direct reprogramming of human somatic cells with OCT4, SOX2, MYC, and KLF4 (Park et al., Nature 2008), and have generated disease-specific iPS cells from patients with a number of hematologic conditions (Park et al., Cell 2008; Agarwal et al., submitted). Applications of disease-specific cells for investigating the mechanisms of reprogramming and for probing aspects of human bone marrow disorders will be discussed. Disclosures Daley: iPierian: Consultancy, Equity Ownership; Epizyme: Consultancy; Solasia: Consultancy; MPM Capital: Consultancy.

scholarly journals Zic3 Is Required for Maintenance of Pluripotency in Embryonic Stem Cells

2007 ◽  
Vol 18 (4) ◽  
pp. 1348-1358 ◽  
Author(s):  
Linda Shushan Lim ◽  
Yuin-Han Loh ◽  
Weiwei Zhang ◽  
Yixun Li ◽  
Xi Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Embryonic Stem ◽  
Es Cell ◽  
Lineage Specification ◽  
Mouse Es Cells

Embryonic stem (ES) cell pluripotency is dependent upon sustained expression of the key transcriptional regulators Oct4, Nanog, and Sox2. Dissection of the regulatory networks downstream of these transcription factors has provided critical insight into the molecular mechanisms that regulate ES cell pluripotency and early differentiation. Here we describe a role for Zic3, a member of the Gli family of zinc finger transcription factors, in the maintenance of pluripotency in ES cells. We show that Zic3 is expressed in ES cells and that this expression is repressed upon differentiation. The expression of Zic3 in pluripotent ES cells is also directly regulated by Oct4, Sox2, and Nanog. Targeted repression of Zic3 in human and mouse ES cells by RNA interference–induced expression of several markers of the endodermal lineage. Notably, the expression of Nanog, a key pluripotency regulator and repressor of extraembryonic endoderm specification in ES cells, was significantly reduced in Zic3 knockdown cells. This suggests that Zic3 may prevent endodermal marker expression through Nanog-regulated pathways. Thus our results extend the ES cell transcriptional network beyond Oct4, Nanog, and Sox2, and further establish that Zic3 plays an important role in the maintenance of pluripotency by preventing endodermal lineage specification in embryonic stem cells.

scholarly journals AIRE is a critical spindle-associated protein in embryonic stem cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Bin Gu ◽  
Jean-Philippe Lambert ◽  
Katie Cockburn ◽  
Anne-Claude Gingras ◽  
Janet Rossant
Keyword(s):  
Molecular Mechanisms ◽  
Function Analysis ◽  
Es Cells ◽  
Embryonic Stem ◽  
Spindle Pole ◽  
Preimplantation Embryos ◽  
Loss Of Function ◽  
Cell Cycles ◽  
Associated Proteins ◽  
Mes Cells

Embryonic stem (ES) cells go though embryo-like cell cycles regulated by specialized molecular mechanisms. However, it is not known whether there are ES cell-specific mechanisms regulating mitotic fidelity. Here we showed that Autoimmune Regulator (Aire), a transcription coordinator involved in immune tolerance processes, is a critical spindle-associated protein in mouse ES(mES) cells. BioID analysis showed that AIRE associates with spindle-associated proteins in mES cells. Loss of function analysis revealed that Aire was important for centrosome number regulation and spindle pole integrity specifically in mES cells. We also identified the c-terminal LESLL motif as a critical motif for AIRE’s mitotic function. Combined maternal and zygotic knockout further revealed Aire’s critical functions for spindle assembly in preimplantation embryos. These results uncovered a previously unappreciated function for Aire and provide new insights into the biology of stem cell proliferation and potential new angles to understand fertility defects in humans carrying Aire mutations.

scholarly journals Research Progress and Application Prospect of IPS Cells

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Ceng Yiwu
Keyword(s):  
Stem Cells ◽  
Es Cells ◽  
Embryonic Stem ◽  
Donor Cell ◽  
Ips Cells ◽  
New Drugs ◽  
Theoretical Research ◽  
Research Progress ◽  
Ips Cell

Differentiated somatic cells can be reprogrammed into induced pluripotent stem cells (iPS cells) by introducingspecific transcription factors. This technique avoids immune rejection and ethical problems in stem cell research.A great revolution in the fi eld of science. As with embryonic stem cells (ES cells), iPS cells are able to self-renewand maintain undiff erentiated state. In vitro, iPS cells can be induced to diff erentiate into a variety of mature cells,therefore, iPS cells in theoretical research and clinical applications are extremely valuable. IPS cell diff erentiationand transplantation in the treatment of blood diseases have a great use, iPS cells can treat nervous system diseases,to provide in vitro disease model, to study the mechanism of disease formation, screening new drugs and thedevelopment of new to provide a new treatment The The use of iPS cells as a nuclear donor cell, with the appropriatereceptor cells after fusion can be directly obtained transgenic animals. Not only can improve the genetic nature ofanimals, but also can break the boundaries of species and get the new animal traits that cannot achieve by usingtraditional mating methods. The research of iPS cells has been widely concerned, and it is the research hotspot in cellbiology and molecular biology. In this paper, the defi nition of iPS cells, the acquisition of iPS cells, the history ofdevelopment, the signifi cance of research, the progress of research, the application of iPS cells, and the problems ofiPS cells were reviewed.

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