Cell Stem Cell

Mendeley Supplemental Figures for Joost et al., 2020. Mendeley Figure S1: Summarized comparison of main and validation dataset. Mendeley Figure S2: Illustrative visualisation of potential receptor-ligand interactions. Mendeley Figure S3: Contribution of biological replicates to 1st and 2nd level clusters visualized on UMAP.

Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a reference framework of the developing and adult human brain. We find that multiple GSC subtypes exist within a single tumor. Within these GSCs, we identify an invasive cell population similar to outer radial glia (oRG), a fetal cell type that expands the stem cell niche in normal human cortex. Using live time-lapse imaging of primary resected tumors, we discover that tumor derived oRG-like cells undergo characteristic mitotic somal translocation behavior previously only observed in human development, suggesting a reactivation of developmental programs. In addition, we show that PTPRZ1 mediates both mitotic somal translocation and glioblastoma tumor invasion. These data suggest that the presence of heterogeneous GSCs may underlie glioblastoma’s rapid progression and invasion. Supplemental Table Legends Supplemental Table 1 (Related to Figure 1). Clinical Annotations and Sequencing Information Clinical annotations of tumor samples as available, including age, sex, diagnosis and karyotypic/mutational information. Sequencing parameters for each sample, including the number of cells, average reads per cell, average genes per cell and method of single-cell capture. Supplemental Table 2 (Related to Figure 1). Cluster Markers Cluster markers and cluster cell type interpretations for each dataset based upon clustering analysis. Supplemental Table 3 (Related to Figure 1 and 3) Exome Sequencing Results Exome sequencing results from 5 tumors. Supplemental Table 4 (Related to Figure 1, 2, 3) Cell Metadata Table of metadata by cell, including cell id, tumor sample, and cell type. Supplemental Table 5 (Related to Figures 5 and 6). Transplantation Single-cell Identification Cluster identity summary for mouse and organoid single-cell experiments. Supplemental Table 6 (Related to Figure 5). PTPRZ1 Knockdown Differentiation Gene Expression Differential gene expression summary with the small hairpin mediated knockdown of PTPRZ1 in primary cortical and primary glioblastoma samples.

Irradiation dose response curves of organoids: data for Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer.

The responses of individual organoid to different treatments (irradiation, 5-Fu and CPT-11): data for Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer.

The raw data of the main figures can be obtained here.

CyTOF permits multidimensional relative protein quantitation in single-cells beyond that possible with flow cytometry and we applied it to mouse bone marrow stromal cells using a customized CyTOF panel. To gauge the likely functional relevance of particular bone marrow stromal cell subsets, we assessed their responses under a clinically relevant stress condition. Patients undergoing bone marrow transplantation are conditioned with myeloablative radiation or chemotherapy. In mice however, this is best modeled by a lethal dose of irradiation. Since the HSPC graft is infused one day after radiation, we assessed stromal populations at that time. In addition we assessed 1 hour after radiation to evaluate early changes.

Data associated with the manuscript published in Cell Stem Cell: Intracellular Ca2+ Homeostasis and Nuclear Export Mediate Exit from Naïve Pluripotency Matthew S. MacDougall, Ryan Clarke, Bradley J. Merrill Included here: Data tables, R scripts, some imaging analysis(4E), and uncropped blot images Not included here for the sake of space: Micrographs and flow cytometry data

Here we demonstrate that not only is hippocampal neurogenesis persistent through the tenth decade of life, but it is detectable even in patients with mild cognitive impairments and Alzheimer’s disease. In a cohort of 18 patients with a mean age of 90.6 years, Nestin+Sox2+Ki67+ neural stem cells and DCX+ neuroblasts and immature neurons were detected, but their number greatly varies between patients. Nestin+ cells localize in the anterior hippocampus while neural progenitor cells, neuroblasts and immature neurons are evenly distributed along the entire anterior/posterior axis. Notably, the number of DCX+PCNA+ cells is reduced in mild cognitive impairments and higher numbers of neuroblasts are associated with better cognitive status. In addition, the number of DCX+PCNA+ cells correlate with the amount of presynaptic SNARE interactions. Our results suggest the existence of hippocampal neurogenesis in the aged and diseased human brain and the possible association of neurogenesis with cognition.

The source data for ~70 panels of data used to compute statistical significance in the paper.

It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD+-boosting agent Nicotinamide Riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD+ boosting strategies on the most primitive blood stem cells, establishes a novel link between HSC mitochondrial stress, mitophagy and stem cell fate decision, and unveils the potential of NR to improve recovery of patients suffering from hematological failure including post-chemo/radiotherapy.