Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA213154 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Herein, we demonstrated that the cell lineage commitment is unexpectedly regulated by the novel functions of H2A.X, a histone variant which was only well-known for its role in genome integrity maintenance previously. Surprisingly, only in ESCs but not differentiated cells, H2A.X is specifically targeted to genomic regions encoding early embryonic and extra-embryonic lineage genes to repress their expression. In addition, H2A.X is also enriched at genomic regions sensitive to replication stress and maintains genomic stability thereat. Most interestingly, faithful H2A.X deposition plays critical roles in maintaining both cell lineage commitment and genome integrity in iPSC. In iPSC lines which support the development of "all-iPS" animals, H2A.X deposition faithfully recapitulates the ESC pattern and therefore, the genome stability and cell lineage commitment are maintained. In iPSC lines that fail to support embryonic development, defective H2A.X depositions result in aberrant upregulation of early embryonic and extra-embryonic lineage genes and H2A.X-dependent genome instability. mRNA-Seq of WT ESC and H2A.X KO ESC; and 4N+, 4N- iPSC.
2014-09-07 | E-GEOD-49147 | biostudies-arrayexpress
Project description:Herein, we demonstrated that the cell lineage commitment is unexpectedly regulated by the novel functions of H2A.X, a histone variant which was only well-known for its role in genome integrity maintenance previously. Surprisingly, only in ESCs but not differentiated cells, H2A.X is specifically targeted to genomic regions encoding early embryonic and extra-embryonic lineage genes to repress their expression. In addition, H2A.X is also enriched at genomic regions sensitive to replication stress and maintains genomic stability thereat. Most interestingly, faithful H2A.X deposition plays critical roles in maintaining both cell lineage commitment and genome integrity in iPSC. In iPSC lines which support the development of "all-iPS" animals, H2A.X deposition faithfully recapitulates the ESC pattern and therefore, the genome stability and cell lineage commitment are maintained. In iPSC lines that fail to support embryonic development, defective H2A.X depositions result in aberrant upregulation of early embryonic and extra-embryonic lineage genes and H2A.X-dependent genome instability.
2014-09-07 | GSE49147 | GEO
Project description:With the advent of the induced pluripotent stem cell (iPSC) technology, how to distinguish the developmental potentials of the iPSC clones with molecular approaches becomes an imperative issue. Herein, we demonstrated that histone variant H2A.X plays an unexpected role in distinguishing the developmental potentials of iPSC. We showed that H2A.X is specifically targeted to and negatively regulates extra-embryonic lineage gene expression in embryonic stem cell (ESCs) and therefore, it prevents trophectoderm (TE) lineage differentiation under inductive conditions. ESC-specific H2A.X deposition and functions are faithfully recapitulated in the iPSC lines that support the development of “all-iPS” animals. In iPSC lines that fail to support embryonic development, aberrant H2A.X depositions result in upregulation of extra-embryonic lineage genes and predisposition to extra-embryonic tissue differentiation. In summary, our work has revealed novel epigenetic mechanisms for maintaining cell lineage commitment, which can be used to distinguish the quality of the iPSC lines. Detect and compare different H2A.X deposition patterns in ES cells [GSE42306] and TS cells, with Illumina HiSeq 2000
2014-09-07 | E-GEOD-57216 | biostudies-arrayexpress
Project description:With the advent of the induced pluripotent stem cell (iPSC) technology, how to distinguish the developmental potentials of the iPSC clones with molecular approaches becomes an imperative issue. Herein, we demonstrated that histone variant H2A.X plays an unexpected role in distinguishing the developmental potentials of iPSC. We showed that H2A.X is specifically targeted to and negatively regulates extra-embryonic lineage gene expression in embryonic stem cell (ESCs) and therefore, it prevents trophectoderm (TE) lineage differentiation under inductive conditions. ESC-specific H2A.X deposition and functions are faithfully recapitulated in the iPSC lines that support the development of “all-iPS” animals. In iPSC lines that fail to support embryonic development, aberrant H2A.X depositions result in upregulation of extra-embryonic lineage genes and predisposition to extra-embryonic tissue differentiation. In summary, our work has revealed novel epigenetic mechanisms for maintaining cell lineage commitment, which can be used to distinguish the quality of the iPSC lines.
2014-09-07 | GSE57216 | GEO
Project description:It is well-known that embryonic stem cells (ESC) are much more sensitive to replication-induced stress than differentiated cells but the underpinning mechanisms are largely unknown. H2A.X, a minor variant of H2A, constitutes only 1-10% of the mammalian genome. H2A.X plays a well-known for role in the DNA damage response and maintaining stability in the genome, including the regions frequently experiencing replication stress, such as the fragile sites. Intriguingly, several recent studies have reported that H2A.X function is elevated in ESC; and others reported that H2A.X function is provoked during cellular reprogramming (in induced pluripotent stem cells, iPSC), indicating that increased proliferation during iPS may trigger replication stress and the H2A.X DNA damage response. However, several studies of genomic instability in iPSC led to different conclusions on this important issue. For example, frequent copy number variants (CNV) were reported at the genomic regions sensitive to replication stress, such as the fragile sites. On the other hand, another study reported the lack of genomic instability in mouse iPS clones that are able to generate “all-iPS” animals in tetraploid complementation assays (4N+ iPSC), indicative of a potential link between pluripotency and genome integrity. However, whether if high level genomic instability occurs in the 4N- iPSC iPSC clones at replication stress sensitive regions is unknown. Moreover, due to the lack of mechanistic insights on genome integrity maintenance, how pluripotency and genome integrity are connected remains elusive. Here we show that H2A.X plays unexpected roles in maintaining pluripotency and genome integrity in ESC and iPSC. In ESC, it is specially enriched at genomic regions sensitive to replication stress so that it protects genome integrity thereat. Faithful H2A.X deposition is critical for genome integrity and pluripotency in iPSC. H2A.X depositions in 4N+ iPSC clones faithfully recapitulate the ESC pattern and therefore, prevent genome instability. On the other hand, insufficient H2A.X depositions in 4N- iPSC clones at such regions lead to genome instability and defects in replication stress response and DNA repair, reminiscent of the H2A.X deficient ESC. Detect and compare different H2A.X deposition patterns in ES cells and iPS cells, with Illumina HiSeq 2000 and Illumina Genome Analyzer IIx
2014-09-07 | E-GEOD-42306 | biostudies-arrayexpress
Project description:It is well-known that embryonic stem cells (ESC) are much more sensitive to replication-induced stress than differentiated cells but the underpinning mechanisms are largely unknown. H2A.X, a minor variant of H2A, constitutes only 1-10% of the mammalian genome. H2A.X plays a well-known for role in the DNA damage response and maintaining stability in the genome, including the regions frequently experiencing replication stress, such as the fragile sites. Intriguingly, several recent studies have reported that H2A.X function is elevated in ESC; and others reported that H2A.X function is provoked during cellular reprogramming (in induced pluripotent stem cells, iPSC), indicating that increased proliferation during iPS may trigger replication stress and the H2A.X DNA damage response. However, several studies of genomic instability in iPSC led to different conclusions on this important issue. For example, frequent copy number variants (CNV) were reported at the genomic regions sensitive to replication stress, such as the fragile sites. On the other hand, another study reported the lack of genomic instability in mouse iPS clones that are able to generate “all-iPS” animals in tetraploid complementation assays (4N+ iPSC), indicative of a potential link between pluripotency and genome integrity. However, whether if high level genomic instability occurs in the 4N- iPSC iPSC clones at replication stress sensitive regions is unknown. Moreover, due to the lack of mechanistic insights on genome integrity maintenance, how pluripotency and genome integrity are connected remains elusive. Here we show that H2A.X plays unexpected roles in maintaining pluripotency and genome integrity in ESC and iPSC. In ESC, it is specially enriched at genomic regions sensitive to replication stress so that it protects genome integrity thereat. Faithful H2A.X deposition is critical for genome integrity and pluripotency in iPSC. H2A.X depositions in 4N+ iPSC clones faithfully recapitulate the ESC pattern and therefore, prevent genome instability. On the other hand, insufficient H2A.X depositions in 4N- iPSC clones at such regions lead to genome instability and defects in replication stress response and DNA repair, reminiscent of the H2A.X deficient ESC. In this study, male 129sv/C57 ES cell genomic DNA was used as reference control, to identify CNV sites in iPS cell lines. And also detect H2A.X (-/-) ES cell (129/Sv) CNVs, with the H2A.X(f/f) ES cell DNA (129/Sv) as control. DNA samples were compared on NimbleGen Mouse CGH 3x720K Whole-Genome Tiling Array (Build MM9).
2014-09-07 | E-GEOD-42266 | biostudies-arrayexpress
Project description:It is well-known that embryonic stem cells (ESC) are much more sensitive to replication-induced stress than differentiated cells but the underpinning mechanisms are largely unknown. H2A.X, a minor variant of H2A, constitutes only 1-10% of the mammalian genome. H2A.X plays a well-known for role in the DNA damage response and maintaining stability in the genome, including the regions frequently experiencing replication stress, such as the fragile sites. Intriguingly, several recent studies have reported that H2A.X function is elevated in ESC; and others reported that H2A.X function is provoked during cellular reprogramming (in induced pluripotent stem cells, iPSC), indicating that increased proliferation during iPS may trigger replication stress and the H2A.X DNA damage response. However, several studies of genomic instability in iPSC led to different conclusions on this important issue. For example, frequent copy number variants (CNV) were reported at the genomic regions sensitive to replication stress, such as the fragile sites. On the other hand, another study reported the lack of genomic instability in mouse iPS clones that are able to generate “all-iPS” animals in tetraploid complementation assays (4N+ iPSC), indicative of a potential link between pluripotency and genome integrity. However, whether if high level genomic instability occurs in the 4N- iPSC iPSC clones at replication stress sensitive regions is unknown. Moreover, due to the lack of mechanistic insights on genome integrity maintenance, how pluripotency and genome integrity are connected remains elusive. Here we show that H2A.X plays unexpected roles in maintaining pluripotency and genome integrity in ESC and iPSC. In ESC, it is specially enriched at genomic regions sensitive to replication stress so that it protects genome integrity thereat. Faithful H2A.X deposition is critical for genome integrity and pluripotency in iPSC. H2A.X depositions in 4N+ iPSC clones faithfully recapitulate the ESC pattern and therefore, prevent genome instability. On the other hand, insufficient H2A.X depositions in 4N- iPSC clones at such regions lead to genome instability and defects in replication stress response and DNA repair, reminiscent of the H2A.X deficient ESC.
2014-09-07 | GSE42266 | GEO
Project description:It is well-known that embryonic stem cells (ESC) are much more sensitive to replication-induced stress than differentiated cells but the underpinning mechanisms are largely unknown. H2A.X, a minor variant of H2A, constitutes only 1-10% of the mammalian genome. H2A.X plays a well-known for role in the DNA damage response and maintaining stability in the genome, including the regions frequently experiencing replication stress, such as the fragile sites. Intriguingly, several recent studies have reported that H2A.X function is elevated in ESC; and others reported that H2A.X function is provoked during cellular reprogramming (in induced pluripotent stem cells, iPSC), indicating that increased proliferation during iPS may trigger replication stress and the H2A.X DNA damage response. However, several studies of genomic instability in iPSC led to different conclusions on this important issue. For example, frequent copy number variants (CNV) were reported at the genomic regions sensitive to replication stress, such as the fragile sites. On the other hand, another study reported the lack of genomic instability in mouse iPS clones that are able to generate “all-iPS” animals in tetraploid complementation assays (4N+ iPSC), indicative of a potential link between pluripotency and genome integrity. However, whether if high level genomic instability occurs in the 4N- iPSC iPSC clones at replication stress sensitive regions is unknown. Moreover, due to the lack of mechanistic insights on genome integrity maintenance, how pluripotency and genome integrity are connected remains elusive. Here we show that H2A.X plays unexpected roles in maintaining pluripotency and genome integrity in ESC and iPSC. In ESC, it is specially enriched at genomic regions sensitive to replication stress so that it protects genome integrity thereat. Faithful H2A.X deposition is critical for genome integrity and pluripotency in iPSC. H2A.X depositions in 4N+ iPSC clones faithfully recapitulate the ESC pattern and therefore, prevent genome instability. On the other hand, insufficient H2A.X depositions in 4N- iPSC clones at such regions lead to genome instability and defects in replication stress response and DNA repair, reminiscent of the H2A.X deficient ESC.
2014-09-07 | GSE42306 | GEO
Project description:H2A.X native ChIP-Seq in ESC and iPSC: Histone Variant H2A.X Mediated Epigenetic Mechanisms are Critical for Maintaining Genome Stability and Pluripotency in ES and iPS Cells
| PRJNA181007 | ENA
Project description:Stem cell fate decisions are tightly regulated by several processes, including epigenetic based histone modifications. Histone variants (HVs) represent a subfamily of epigenetic regulators implicated in early embryonic development, but their role in stem cell fate control has not been targeted. Here we reveal direct involvement of phosphorylation state of the histone variant H2A.X that allows control of self-renewal and differentiation of human pluripotent stem cells (hPSCs) and leukemic patient derived progenitors. Reduced levels of γH2A.X using either genetic approaches or chemical targeting allowed enhanced hPSC differentiation toward the mesodermal (hematopoietic) lineage with concomitant inhibition of ectodermal (neural) development. In contrast, activation and sustained levels of phosphorylated H2A.X enhanced hPSC ectodermal fate while suppressing mesodermal derived hematopoiesis. This controlled bifurcation of neural vs. hematopoietic differentiation correlated to occupancy of γH2A.X at gene loci associated with lineage selection. Drug modulation of H2A.X phosphorylation was extended to somatic cells to reveal the ability to induce differentiation of leukemic progenitors and serve as a biomarker in a cohort of adult leukemic patients. Our study uncovers a mechanism of cell-fate control of hPSCs extended to neoplastic progenitors through a histone variant epigenetic regulation
2021-03-09 | GSE164680 | GEO