Faculty Opinions recommendation of H2AZ is enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment.

2009 ◽  
Author(s):  
Leonie Ringrose
Keyword(s):  
Target Genes ◽  
Es Cells ◽  
Lineage Commitment ◽  
Complex Target ◽  
Polycomb Complex

scholarly journals H2AZ Is Enriched at Polycomb Complex Target Genes in ES Cells and Is Necessary for Lineage Commitment

Cell ◽  
2008 ◽  
Vol 135 (4) ◽  
pp. 649-661 ◽  
Author(s):  
Menno P. Creyghton ◽  
Styliani Markoulaki ◽  
Stuart S. Levine ◽  
Jacob Hanna ◽  
Michael A. Lodato ◽  
...  
Keyword(s):  
Target Genes ◽  
Es Cells ◽  
Lineage Commitment ◽  
Complex Target ◽  
Polycomb Complex

scholarly journals Steroidogenic Factor-1 (SF-1)-Driven Differentiation of Murine Embryonic Stem (ES) Cells into a Gonadal Lineage

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2870-2882 ◽  
Author(s):  
Unmesh Jadhav ◽  
J. Larry Jameson
Keyword(s):  
Target Genes ◽  
De Novo ◽  
Embryoid Body ◽  
Es Cells ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Culture Conditions ◽  
Steroidogenic Factor 1 ◽  
Lineage Differentiation ◽  
And Function

Steroidogenic factor 1 (SF-1) is essential for the development and function of steroidogenic tissues. Stable incorporation of SF-1 into embryonic stem cells (SF-1-ES cells) has been shown to prime the cells for steroidogenesis. When provided with exogenous cholesterol substrate, and after treatment with retinoic acid and cAMP, SF-1-ES cells produce progesterone but do not produce other steroids such as cortisol, estradiol, or testosterone. In this study, we explored culture conditions that optimize SF-1-mediated differentiation of ES cells into defined steroidogenic lineages. When embryoid body formation was used to facilitate cell lineage differentiation, SF-1-ES cells were found to be restricted in their differentiation, with fewer cells entering neuronal pathways and a larger fraction entering the steroidogenic lineage. Among the differentiation protocols tested, leukemia inhibitory factor (LIF) removal, followed by prolonged cAMP treatment was most efficacious for inducing steroidogenesis in SF-1-ES cells. In this protocol, a subset of SF-1-ES cells survives after LIF withdrawal, undergoes morphologic differentiation, and recovers proliferative capacity. These cells are characterized by induction of steroidogenic enzyme genes, use of de novo cholesterol, and production of multiple steroids including estradiol and testosterone. Microarray studies identified additional pathways associated with SF-1 mediated differentiation. Using biotinylated SF-1 in chromatin immunoprecipitation assays, SF-1 was shown to bind directly to multiple target genes, with induction of binding to some targets after steroidogenic treatment. These studies indicate that SF-1 expression, followed by LIF removal and treatment with cAMP drives ES cells into a steroidogenic pathway characteristic of gonadal steroid-producing cells.

scholarly journals Differences in Gene Expression between Wild Type and Hoxa1 Knockout Embryonic Stem Cells after Retinoic Acid Treatment or Leukemia Inhibitory Factor (LIF) Removal

2005 ◽  
Vol 280 (16) ◽  
pp. 16484-16498 ◽  
Author(s):  
Eduardo Martinez-Ceballos ◽  
Pierre Chambon ◽  
Lorraine J. Gudas
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Retinoic Acid ◽  
Leukemia Inhibitory Factor ◽  
Target Genes ◽  
Hox Genes ◽  
Es Cells ◽  
Embryonic Stem ◽  
Inhibitory Factor ◽  
Hoxa Cluster

Homeobox (Hox) genes encode a family of transcription factors that regulate embryonic patterning and organogenesis. In embryos, alterations of the normal pattern of Hox gene expression result in homeotic transformations and malformations. Disruption of theHoxa1gene, the most 3′ member of the Hoxa cluster and a retinoic acid (RA) direct target gene, results in abnormal ossification of the skull, hindbrain, and inner ear deficiencies, and neonatal death. We have generated Hoxa1-/-embryonic stem (ES) cells (named Hoxa1-15) from Hoxa1-/-mutant blastocysts to study the Hoxa1 signaling pathway. We have characterized in detail these Hoxa1-/-ES cells by performing microarray analyses, and by this technique we have identified a number of putative Hoxa-1 target genes, including genes involved in bone development (e.g. Col1a1,Postn/Osf2, and the bone sialoprotein gene orBSP), genes that are expressed in the developing brain (e.g. Nnat,Wnt3a,BDNF,RhoB, andGbx2), and genes involved in various cellular processes (e.g. M-RAS,Sox17,Cdkn2b,LamA1,Col4a1,Foxa2,Foxq1,Klf5, andIgf2). Cell proliferation assays and Northern blot analyses of a number of ES cell markers (e.g. Rex1,Oct3/4,Fgf4, andBmp4) suggest that the Hoxa1 protein plays a role in the inhibition of cell proliferation by RA in ES cells. Additionally, Hoxa1-/-ES cells express high levels of various endodermal markers, includingGata4andDab2, and express much lessFgf5after leukemia inhibitory factor (LIF) withdrawal. Finally, we propose a model in which the Hoxa1 protein mediates repression of endodermal differentiation while promoting expression of ectodermal and mesodermal characteristics.

Abstract 356: Scl Represses Cardiogenesis via Distant Enhancers during Hemogenic Endothelium Specification

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Tonis Org ◽  
Dan Duan ◽  
Roberto Ferrari ◽  
Amelie Montel-Hagen ◽  
Ben Van Handel ◽  
...  
Keyword(s):  
Target Genes ◽  
Es Cells ◽  
Bhlh Transcription Factor ◽  
Hemogenic Endothelium ◽  
Master Regulator ◽  
Critical Function ◽  
Hematopoietic Stem ◽  
Mesoderm Development ◽  
Chip Sequencing ◽  
Mouse Es Cells

Understanding the mechanisms directing mesoderm specification holds a great potential to advance the development of cell-based therapies for cardiovascular and blood disorders. The bHLH transcription factor Scl is known as the master regulator of the hematopoietic fate. We recently discovered that, in addition to its critical function in promoting the establishment of hemogenic endothelium during hematopoietic stem/progenitor cell (HS/PC) development, Scl is also required to repress cardiomyogenesis in endothelium in hematopoietic tissues and endocardium in the heart. However, the mechanisms for the cardiac repression have remained unknown. Using ChIP-sequencing and microarray analysis of Flk+ mesoderm differentiated from mouse ES cells, we show that Scl both directly activates a broad gene regulatory network required for hemogenic endothelium and HS/PC development (e.g. Runx1, cMyb, Lyl1, Mef2C, Sox7 etc.), and directly represses transcriptional regulators required for cardiogenesis (e.g. Gata4, Gata6, Myocd, etc.) and mesoderm development (Eomes, Mixl1, Etv2, etc.). Repression of cardiac and mesodermal programs occurs during a short developmental window through Scl binding to distant enhancers, while binding to hematopoietic regulators extends throughout HS/PC and red blood cell development and encompasses both distant and proximal binding sites. We also discovered that, surprisingly, Scl complex partners Gata 1 and 2 are dispensable for hematopoietic vs. cardiac specification and Scl binding to majority of its target genes. Nevertheless, Gata factors co-operate with Scl to activate selected transcription factors that facilitate HS/PC emergence from hemogenic endothelium. These results denote Scl as a true master regulator of hematopoietic vs. cardiac fate choice and suggest a mechanism by which lineage-specific bHLH factors direct the divergence of competing fates.

scholarly journals Caspase-8, receptor-interacting protein kinase 1 (RIPK1), and RIPK3 regulate retinoic acid-induced cell differentiation and necroptosis

2019 ◽  
Vol 27 (5) ◽  
pp. 1539-1553 ◽  
Author(s):  
Masataka Someda ◽  
Shunsuke Kuroki ◽  
Hitoshi Miyachi ◽  
Makoto Tachibana ◽  
Shin Yonehara
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Protein Kinase ◽  
Target Genes ◽  
Es Cells ◽  
Embryoid Bodies ◽  
Embryonic Lethality ◽  
Caspase 8 ◽  
Interacting Protein ◽  
Specific Target

Abstract Among caspase family members, Caspase-8 is unique, with associated critical activities to induce and suppress death receptor-mediated apoptosis and necroptosis, respectively. Caspase-8 inhibits necroptosis by suppressing the function of receptor-interacting protein kinase 1 (RIPK1 or RIP1) and RIPK3 to activate mixed lineage kinase domain-like (MLKL). Disruption of Caspase-8 expression causes embryonic lethality in mice, which is rescued by depletion of either Ripk3 or Mlkl, indicating that the embryonic lethality is caused by activation of necroptosis. Here, we show that knockdown of Caspase-8 expression in embryoid bodies derived from ES cells markedly enhances retinoic acid (RA)-induced cell differentiation and necroptosis, both of which are dependent on Ripk1 and Ripk3; however, the enhancement of RA-induced cell differentiation is independent of Mlkl and necrosome formation. RA treatment obviously enhanced the expression of RA-specific target genes having the retinoic acid response element (RARE) in their promoter regions to induce cell differentiation, and induced marked expression of RIPK1, RIPK3, and MLKL to stimulate necroptosis. Caspase-8 knockdown induced RIPK1 and RIPK3 to translocate into the nucleus and to form a complex with RA receptor (RAR), and RAR interacting with RIPK1 and RIPK3 showed much stronger binding activity to RARE than RAR without RIPK1 or RIPK3. In Caspase-8-deficient as well as Caspase-8- and Mlkl-deficient mouse embryos, the expression of RA-specific target genes was obviously enhanced. Thus, Caspase-8, RIPK1, and RIPK3 regulate RA-induced cell differentiation and necroptosis both in vitro and in vivo.

The H19 induction triggers trophoblast lineage commitment in mouse ES cells

2013 ◽  
Vol 436 (2) ◽  
pp. 313-318 ◽  
Author(s):  
Hiroaki Fujimori ◽  
Hiroaki Mukai ◽  
Yasufumi Murakami ◽  
Myriam Hemberger ◽  
Yoshitaka Hippo ◽  
...  
Keyword(s):  
Es Cells ◽  
Lineage Commitment ◽  
Mouse Es Cells

Switching genes on and off in haemopoiesis

2008 ◽  
Vol 36 (4) ◽  
pp. 613-618 ◽  
Author(s):  
David Garrick ◽  
Marco De Gobbi ◽  
Magnus Lynch ◽  
Douglas R. Higgs
Keyword(s):  
Stem Cells ◽  
Histone Deacetylases ◽  
Gene Locus ◽  
Molecular Mechanisms ◽  
Terminal Differentiation ◽  
Lineage Commitment ◽  
Clinical Settings ◽  
Globin Genes ◽  
Specific Manner ◽  
Polycomb Complex

At present, the molecular mechanisms by which stem cells commit to and differentiate towards specific lineages are poorly characterized, and will need to be better understood before stem cells can be exploited fully in experimental and clinical settings. Transcriptional regulation, the ability to turn genes on and off, lies at the heart of these processes of lineage commitment and specification. We have focused on fully understanding how these decisions are made at a single mammalian gene locus, the α-globin genes, which become up-regulated in a tissue- and developmental-stage specific manner during haemopoiesis. The studies summarized in the present article have revealed that complete regulation of this gene cluster involves not only activating mechanisms in expressing erythroid cells, but also repressing mechanisms, involving the Polycomb complex and histone deacetylases which are present in non-erythroid tissues. Taken together, these observations provide a well-characterized model of how gene expression is fully regulated during the transition from stem cells through lineage commitment and terminal differentiation.

scholarly journals Thyroid Hormone-Dependent Gene Expression in Differentiated Embryonic Stem Cells and Embryonal Carcinoma Cells: Identification of Novel Thyroid Hormone Target Genes by Deoxyribonucleic Acid Microarray Analysis

Endocrinology ◽  
2005 ◽  
Vol 146 (2) ◽  
pp. 776-783 ◽  
Author(s):  
Yan-Yun Liu ◽  
Gregory A. Brent
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Thyroid Hormone ◽  
Early Development ◽  
Target Genes ◽  
Es Cells ◽  
Embryonic Stem ◽  
Wild Type ◽  
Ec Cells

Abstract T3 is required for normal early development, but relatively few T3-responsive target genes have been identified. In general, in vitro stem cell differentiation techniques stimulate a wide range of developmental programs, including thyroid hormone receptor (TR) pathways. We developed several in vitro stem cell models to more specifically identify TR-mediated gene expression in early development. We found that embryonic carcinoma (EC) cells have reduced T3 nuclear binding capacity and only modestly express the known T3 target genes, neurogranin (RC3) and Ca2+/calmodulin-dependent protein kinase IV (CaMKIV), in response to T3. Full T3 induction in transient transfection of EC cells was restored with cotransfection of a TR expression vector. We, therefore, performed gene expression profiles in wild-type embryonic stem (ES) cells compared with expression in cells with deficient (EC) or mutant TR (TRα P398H mutant ES cells), to identify T3 target genes. T3 stimulation of wild-type ES cells altered mRNA expression of 610 known genes (26% of those studied), although only approximately 60 genes (1%) met criteria for direct T3 stimulation based on the magnitude of induction and requirement for the presence of TR. We selected five candidate T3 target genes, neurexophilin 2, spermatid perinuclear RNA-binding protein (SPNR), kallikrein-binding protein (KBP), prostate-specific membrane antigen (PSMA), and synaptotagmin II, for more detailed study. T3 responsiveness of these genes was evaluated in both in vitro endogenous gene expression and in vivo mouse model systems. These genes identified in a novel stem cell system, including those induced and repressed in response to T3, may mediate thyroid hormone actions in early development.

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