Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Histone variants (HVs) are a subfamily of epigenetic regulators implicated in embryonic development, but their role in human stem cell fate remains unclear. Here, we reveal that the phosphorylation state of the HV H2A.X (γH2A.X) regulates self-renewal and differentiation of human pluripotent stem cells (hPSCs) and leukemic progenitors. As demonstrated by CRISPR-Cas deletion, H2A.X is essential in maintaining normal hPSC behavior. However, reduced levels of γH2A.X enhances hPSC differentiation toward the hematopoietic lineage with concomitant inhibition of neural development. In contrast, activation and sustained levels of phosphorylated H2A.X enhance hPSC neural fate while suppressing hematopoiesis. This controlled lineage bias correlates to occupancy of γH2A.X at genomic loci associated with ectoderm versus mesoderm specification. Finally, drug modulation of H2A.X phosphorylation overcomes differentiation block of patient-derived leukemic progenitors. Our study demonstrates HVs may serve to regulate pluripotent cell fate and that this biology could be extended to somatic cancer stem cell control.
Pubmed ID: 33691101
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Computable knowledge regarding functions of genes and gene products. GO resources include biomedical ontologies that cover molecular domains of all life forms as well as extensive compilations of gene product annotations to these ontologies that provide largely species-neutral, comprehensive statements about what gene products do. Used to standardize representation of gene and gene product attributes across species and databases.
View all literature mentionsSystem that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsSoftware to graphically browse results of clustering and other analyses from Cluster.
View all literature mentionsSoftware R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.
View all literature mentionsUltrafast and memory efficient tool for aligning sequencing reads to long reference sequences. Supports gapped, local, and paired end alignment modes. More suited to finding longer, gapped alignments in comparison with original Bowtie method.
View all literature mentionsThis polyclonal targets gamma H2A.X (phospho S139)
View all literature mentionsThis monoclonal targets MDC1
View all literature mentionsThis monoclonal targets MRE11
View all literature mentionsThis monoclonal targets GAPDH antibody [6C5]
View all literature mentionsThis monoclonal targets TRA-1-60 Antigen
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets 53BP1
View all literature mentionsThis monoclonal targets HA Tag
View all literature mentionsThis monoclonal targets Histone H2A.X pSer139
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis polyclonal targets Histone H2A.X
View all literature mentionsThis monoclonal targets Phospho-ATM (Ser1981)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets CD45
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis monoclonal targets CD117 (c-Kit)
View all literature mentionsThis unknown targets SSEA-3
View all literature mentionsThis monoclonal targets TRA-1-60 Antigen
View all literature mentions