Single-cell RNA-sequencing reveals Transcriptional Changes and Clonal Architecture associated with Post-Transplant Relapse in Acute Myeloid Leukemia

"Acute myeloid leukemia (AML) is a malignancy characterized by overproduction of myeloid precursors at the expense of more differentiated, functional hematopoietic cells, resulting in anemia, thrombocytopenia, and neutropenia. Despite initial sensitivity to chemotherapy, a majority of patients with AML ultimately relapse. Among the challenges associated with relapse, post-allogeneic stem cell transplant relapse is particularly intractable because of our relative lack of understanding - and thus lack of effective treatment options - of the underlying mechanisms."--IntroductionZiheng Xu (1), Christopher A. Miller (2, 3), Sridhar N. Srivatsan (2), Catrina C. Fronick (3), Robert S. Fulton (3), Timothy J. Ley (2, 3, 4), and Allegra A. Petti (2, 3) ; 1. Washington University School of Medicine. 2. Division of Oncology, Washington University School of Medicine. 3. McDonnell Genome Institute, Washington University School of Medicine. 4. Department of Genetics, Washington University School of Medicine.Includes bibliographical reference

Sequence analysis in Bos taurus reveals pervasiveness of X–Y arms races in mammalian lineages

Studies of Y Chromosome evolution have focused primarily on gene decay, a consequence of suppression of crossing-over with the X Chromosome. Here, we provide evidence that suppression of X-Y crossing-over unleashed a second dynamic: selfish X-Y arms races that reshaped the sex chromosomes in mammals as different as cattle, mice, and men. Using super-resolution sequencing, we explore the Y Chromosome o

Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline

Mapping genome-wide data to human subtelomeres has been problematic due to the incomplete assembly and challenges of low-copy repetitive DNA elements. Here, we provide updated human subtelomere sequence assemblies that were extended by filling telomere-adjacent gaps using clone-based resources. A bioinformatic pipeline incorporating multiread mapping for annotation of the updated assemblies using short-read data sets was developed and implemented. Annotation of subtelomeric sequence features as well as mapping of CTCF and cohesin binding sites using ChIP-seq data sets from multiple human cell types confirmed that CTCF and cohesin bind within 3 kb of the start of terminal repeat tracts at many, but not all, subtelomeres. CTCF and cohesin co-occupancy were also enriched near internal telomere-like sequence (ITS) islands and the nonterminal boundaries of subtelomere repeat elements (SREs) in transformed lymphoblastoid cell lines (LCLs) and human embryonic stem cell (ES) lines, but were not significantly enriched in the primary fibroblast IMR90 cell line. Subtelomeric CTCF and cohesin sites predicted by ChIP-seq using our bioinformatics pipeline (but not predicted when only uniquely mapping reads were considered) were consistently validated by ChIP-qPCR. The colocalized CTCF and cohesin sites in SRE regions are candidates for mediating long-range chromatin interactions in the transcript-rich SRE region. A public browser for the integrated display of short-read sequence–based annotations relative to key subtelomere features such as the start of each terminal repeat tract, SRE identity and organization, and subtelomeric gene models was established