Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. Here we discover that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Furthermore, genetic and pharmacological inhibition of EZH2 decreases the repopulating potential of p53 mutant HSPCs. Thus, we uncover an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations

Author Correction: Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Revealing Spatial–Temporal Patterns of Sea Surface Temperature in the South China Sea Based on Spatial–Temporal Co-Clustering

To discover the spatial–temporal patterns of sea surface temperature (SST) in the South China Sea (SCS), this paper proposes a spatial–temporal co-clustering algorithm optimized by information divergence. This method allows for the clustering of SST data simultaneously across temporal and spatial dimensions and is adaptable to large volumes of data and anomalous data situations. First, the SST data are initially clustered using the co-clustering algorithm. Second, we use information divergence as the loss function to refine the clustering results iteratively. During the iterative optimization of spatial clustering results, we treat the temporal dimension as a constraint; similarly, during the iterative optimization of temporal clustering, we treat the spatial dimension as a constraint. This is to ensure better robustness of the algorithm. Finally, this paper conducts experiments in the SCS to verify our algorithm. According to the analysis of the experimental results, we have drawn the following conclusions. First, the use of the spatial–temporal co-clustering algorithm reveals that the SST in the SCS exhibits strong seasonal patterns in the temporal clustering results. The spatial distribution of SST varies significantly in different seasons. There is a slight difference in SST between the northern and southern regions of the SCS in winter, but the largest difference is in summer. Second, during ocean anomalies, our proposed algorithm can identify the corresponding abnormal patterns. When ENSO occurs, the seasonal distribution pattern of SST in the SCS is destroyed and replaced by an abnormal temporal pattern. The results indicate that during ENSO events, the SST in specific months in the SCS exhibits a correlation with the SST observed 4–5 months afterward

WDR68 is essential for the transcriptional activation of the PRC1-AUTS2 complex and neuronal differentiation of mouse embryonic stem cells

Recent studies on Polycomb repressive complexes (PRC) reveal a surprising role in transcriptional activation, yet the underlying mechanism remains poorly understood. We previously identified a type 1 PRC (PRC1) that contains Autism Susceptibility Candidate 2 (AUTS2), which positively regulates transcription of neuronal genes. However, the mechanism by which the PRC1-AUTS2 complex influences neurodevelopment is unclear. Here we demonstrate that WDR68 is not only an integral component of the PRC1-AUTS2 complex, but it is also required for PRC1-AUTS2-mediated transcription activation. Furthermore, deletion of Wdr68 in mouse embryonic stem cells leads to defects in neuronal differentiation without affecting self-renewal. Through transcriptomic analysis, we found that many genes responsible for neuronal differentiation are down-regulated in Wdr68 deficient neural progenitors. These genes include those targeted by the PRC1-AUTS2 complex. In summary, our studies uncovered a previously unknown but essential component of the active PRC1 complex and evidence of its role in regulating the expression of genes that are important for neuronal differentiation. Keywords: Epigenetics, Stem cells, Transcription, Polycomb, Protein complex, Differentiatio

d3b-center/OpenPedCan-analysis: v2.1.0

<h2>What's Changed</h2> <ul> <li>remove hardlinking and check from old release in data download script by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/358</li> <li>update Table S1 - histologies README by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/357</li> <li>Update to R version 4.2.3 in docker image by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/360</li> <li>Refactoring molecular-subtyping-ATRT module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/359</li> <li>remove snv consensus module "snv-callers" by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/370</li> <li>update tmb-calculation README by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/371</li> <li>Refactoring molecular-subtyping-CRANIO module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/362</li> <li>Refactoring molecular-subtyping-EWS module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/364</li> <li>Refactoring molecular-subtyping-EPN module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/363</li> <li>Refactoring molecular-subtyping-chordoma module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/366</li> <li>Refactoring molecular-subtyping-neurocytoma module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/365</li> <li>Rerun all of the modules with the new docker image by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/372</li> <li>Add methyl probe annotations liftover process description by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/378</li> <li>add deconstructSigs v1.9 by @rjcorb in https://github.com/d3b-center/OpenPedCan-analysis/pull/377</li> <li>:rewind: make new temp module for cnv consensus with manta by @sickler-alex in https://github.com/d3b-center/OpenPedCan-analysis/pull/379</li> <li>Updating module per latest v12 successful run on HPC by @sangeetashukla in https://github.com/d3b-center/OpenPedCan-analysis/pull/381</li> <li> Fixes bug with GNT in which the broad histology was maintained as LGG instead of GNT by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/382</li> <li>Include data release process in the repo README by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/376</li> <li>updated Readme by @atlas4213 in https://github.com/d3b-center/OpenPedCan-analysis/pull/383</li> <li>Update data release analysis process workflow scripts by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/380</li> <li>Updated analysis: missing NBL samples in histologies file by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/367</li> <li>add issue template by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/384</li> <li>update mutational signatures module by @rjcorb in https://github.com/d3b-center/OpenPedCan-analysis/pull/300</li> <li>Update README.md by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/405</li> <li>Update CI subset files to include rmats by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/406</li> <li>Clarify SNV callers included in intersect bed for WGS samples by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/408</li> <li>Add script to download methyl files by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/415</li> <li>Analysis update: remove MTP section from github CI file by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/429</li> <li>Updated analysis: copy_number_consensus_call_manta to use only samples which do not have GATK CNV by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/410</li> <li>enrich cnv non-GATK samples by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/431</li> <li>Create CODEOWNERS by @devbyaccident in https://github.com/d3b-center/OpenPedCan-analysis/pull/436</li> <li>Rerun TMB calculation - test run by @AntoniaChroni in https://github.com/d3b-center/OpenPedCan-analysis/pull/435</li> <li>Analysis update: change LGG methylation subtyping by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/433</li> <li>Analysis Update: merge cnv files by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/419</li> <li>Analysis update: Reduce docker size by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/440</li> <li>Create methyl array probes annotation module by @ewafula in https://github.com/d3b-center/OpenPedCan-analysis/pull/411</li> <li> Change build and run analysis conditions by @devbyaccident in https://github.com/d3b-center/OpenPedCan-analysis/pull/445</li> <li>Updated analysis: sample 7316-4463 HGG subtyping bug by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/412</li> <li>Analysis update: add K28I mutation into subtyping by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/439</li> <li>Update analysis: Fix a typo in molecular_subtyping_HGG script by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/446</li> <li>Analysis update: Organize Dockerfile and reduce docker size by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/447</li> <li>Update focal-cn-file-preparation README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/457</li> <li>Analysis Update: Add neurocytoma workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/466</li> <li>Analysis Update: Add ATRT subtyping workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/467</li> <li>Analysis update: Add CRANIO subtyping workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/464</li> <li>Analysis update: add DMG, EGFR to methyl mol subtype by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/451</li> <li>Analysis Update: Add EWS subtyping workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/465</li> <li>Update analysis: Update age cutoff for CRANIO, PAP by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/472</li> <li>Analysis update: Add workflow for HGG molecular subtyping by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/454</li> <li>Analysis update: Add NBL workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/462</li> <li>Analysis update: Add EPN workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/461</li> <li>Analysis update: Add MB workflow by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/460</li> <li>Add workflow to LGG README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/458</li> <li>Analysis update: Add embryonal workflow to README by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/463</li> <li>update cancer group by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/453</li> <li>add PXA to molecular subtype by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/450</li> <li>Change the output format in molecular-subtyping-HGG module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/374</li> <li>New Analysis: add Pineoblastoma subtype module by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/476</li> <li>add exclude path diagnosis of PB in EMB subtyping module by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/479</li> <li>update readmes for deprecated modules, remove unused modules by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/481</li> <li>update TP53 module/fix HGG discrepancies (2/2) by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/478</li> <li>V12 subset enrich for samples with TP53 SV (1/2) by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/480</li> <li>Analysis update: Incorporate the feedback of HOPE non-HGG samples for v13 by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/484</li> <li>(21/21) Subset v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/531</li> <li>(20/N) Independent specimens v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/530</li> <li>(19/N) Integrate/histology v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/529</li> <li>(18/N) Pathology v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/528</li> <li>(17/N) NBL v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/527</li> <li>(16/N) LGG v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/526</li> <li>(15/N) HGG v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/525</li> <li>(14/N) Pineoblastoma v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/524</li> <li>(13/N) ATRT v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/523</li> <li>(12/N) Neurocytoma v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/522</li> <li>(11/N) EWS v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/521</li> <li>(10/N) Chordoma v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/520</li> <li>(9/N) Embryonal v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/519</li> <li>(8/N) EPN v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/518</li> <li>(6-7/N) MB and CRANIO v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/517</li> <li>(5/N) TP53 v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/516</li> <li>(4-D/N) GSVA v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/515</li> <li>(4-C/N) TMB v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/514</li> <li>(4-B/N) update and run fusion summary by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/513</li> <li>(4-A/N) Focal CN v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/512</li> <li>(3-B/N) GISTIC v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/510</li> <li>(3-A/N) Indep filt fus v13 by @jharenza in https://github.com/d3b-center/OpenPedCan-analysis/pull/509</li> <li>(3/N) v13 release: Run consensus CNV modules for v13 release by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/485</li> <li>(2/N) V13 release: pre-release QC for v13 data by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/473</li> <li>(1/N) v13 release: Update download script and release note by @zzgeng in https://github.com/d3b-center/OpenPedCan-analysis/pull/474</li> </ul> <h2>New Contributors</h2> <ul> <li>@AntoniaChroni made their first contribution in https://github.com/d3b-center/OpenPedCan-analysis/pull/435</li> </ul> <p><strong>Full Changelog</strong>: https://github.com/d3b-center/OpenPedCan-analysis/compare/v2.0.0...v2.1.0</p&gt