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opencc-by-4.0Aug 2024View details →

Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets

Contains the input data used in the analysis of the paper: Aging is associated with functional and molecular changes in distinct hematopoietic stem cell subsets (Su, Hauenstein, Somuncular et al., Nature Communications, 2024).

opencc-by-4.0Sep 2024View details →

Efficient improvement of the proliferation, differentiation, and anti-arthritic capacity of mesenchymal stem cells by simply culturing on the immobilized FGF2 derived peptide, 44-ERGVVSIKGV-53

All data needed to evaluate the results presented in the paper: Soo Bin Lee, Ahmed Abdal Dayem, Sebastian Kmiecik, Kyung Min Lim, Dong Sik Seo, Hyeong-Taek Kim, Polash Kumar Biswas, Minjae Do, Deok-Ho Kim, Ssang-Goo Cho, Efficient improvement of the proliferation, differentiation, and anti-arthritic capacity of mesenchymal stem cells by simply culturing on the immobilized FGF2 derived peptide, 44-ERGVVSIKGV-53, Journal of Advanced Research, Volume 62, 2024, Pages 119-141, ISSN 2090-1232, https://doi.org/10.1016/j.jare.2023.09.041.

opencc-by-4.0Oct 2024View details →

The Regulation of Microglia Activity and the Production of IL-1α and IL-6 in the Degenerated Retina by Mesenchymal Stem Cells

Activation of immune response and production of proinflammatory factors plays an important role in the development and progression of retinal degenerative diseases (RDD). For this reason, focusing on immunomodulation is potential option for the efficient ophthalmological therapy. Mesenchymal stem cells (MSCs) have been study in the treatment of RDD mainly due to their regenerative and neuroprotective actions. Nevertheless, MSCs also possess several immunomodulatory properties. Our study shows that NaIO3-induced degeneration increased in vitro and in vivo expression of genes for Interleukin (IL)-1α and IL-6 in the mouse retinal tissue. In addition, intraperitoneal application of NaIO3 increased expression of gene for Iba-1 and infiltration of CD45+CD11b+ cells into the retina. CD45+ population was also responsible for the production of IL-1α while IL-6 was produced by CD45- cells. Cocultivation of degenerated retina in the presence of MSCs decreased the expression and production of both studied cytokines and expression of gene for Iba-1 in the retinal tissue. On contrary, it was observed that MSCs treated with supernatant from degenerated retina increased the expression of genes for cyclooxygenase-2, transforming growth factor-β, programmed-death ligand 1 and nerve growth factor. These results show that MSCs are able to regulate immune reaction in the degenerated retinal environment.

opencc-byJul 2021View details →

PKHhigh/CD133+/CD24− Renal Stem-Like Cells Isolated from Human Nephrospheres Exhibit In Vitro Multipotency.

The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, but it is difficult to argue whether these populations have the same capacities that have been described in mice. Using the nephrosphere (NS) model, we isolated the quiescent population of adult human renal stem-like PKHhigh/CD133+/CD24− cells (RSC). The aim of this study was to deepen the RSC in vitro multipotency capacity. RSC, not expressing endothelial markers, generated secondary nephrospheres containing CD31+/vWf+ cells and cytokeratin positive cells, indicating the coexistence of endothelial and epithelial commitment. RSC cultured on decellularized human renal scaffolds generated endothelial structures together with the proximal and distal tubular structures. CD31+ endothelial committed progenitors sorted from nephrospheres generated spheroids with endothelial-like sprouts in Matrigel. We also demonstrated the double commitment toward endothelial and epithelial lineages of single RSC. The ability of the plastic RSC population to recapitulate the development of tubular epithelial and endothelial renal lineages makes these cells a good tool for the creation of organoids with translational relevance for studying the parenchymal and endothelial cell interactions and developing new therapeutic strategies.

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Highly-multiplexed mass cytometry screen of human bone marrow hematopoietic stem and progenitor cells

In contrast to the rich single-cell transcriptomic and epigenetic data, the corresponding protein level information of human hematopoietic stem and progenitor cell (HSPC) populations is still missing. We used a highly-multiplexed single-cell screen to quantify the protein expression of 353 surface molecules and 79 functional intracellular molecules (TFs, chromatin regulators, and metabolic enzymes) with mass cytometry. In doing this, we created a core panel with probes against functional protein molecules associated with specific lineage potentials to better illuminate the differentiation potentials of the progenitors. In total, we analyzed 556,226 CD34+ bone marrow HSPCs across three individuals. Our analysis identified ten distinct clusters among HSPCs by unsupervised method and defined their unique proteomic composition. We compare our data-driven populations to the canonical HSPC cell types identified by cell surface proteins and observe discrepancies, especially in the lympho-myeloid axis. Overall, we supply a quantified summary of the proteomes of human HSPCs and create a framework to redefine progenitor populations with unique functional states along hematopoiesis.

opencc-zeroNov 2022View details →

opencc-by-4.0Nov 2022View details →

Diagnostic algorithm for surgical management of limbal stem cell deficiency

Supplementary material (tables) for the article entitled "Diagnostic algorithm for surgical management of limbal stem cell deficiency".

[Data S2] Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

Data S2. GLIPH2 hits for all recipient pairs amongst B6 to B6D2F1 transplants with or without antibiotic exposure and 900cGy vs. 1300cGy TBI conditioning. For all TCRs within each recipient pair (12 mice total, 66 pairs for spleen; 15 pairs for SILP analysis), GLIPH2 specificity groups are generated as described in methods.

[Data S1] Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

Data S1. ALICE hits for all recipient pairs amongst B6 to B6D2F1 transplants with or without antibiotic exposure and 900cGy vs. 1300cGy TBI conditioning. For each recipient pair (12 mice total, 66 pairs for spleen; 15 pairs for SILP analysis), all ALICE hits generated as described in methods.

[Github Sample Dataset] Microbiota dictate T cell clonal selection to promote graft-vs-host disease after stem cell transplantation

[Github Sample Dataset]. This is an accompanying data set for the github repository "https://github.com/acyeh-lab/2023/tree/main/tcr-simulation" referred to in "Non-genetic determinants of clonotypic T cell expansion following stem cell transplantation" by Yeh AC et al.

opencc-zeroJan 2023View details →

dryad36/100

A longitudinal study of DNA and RNA viruses plasma detection in allogeneic hematopoietic stem cell transplant recipients

Background: Viral infections are among the most common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can be associated with transient or sustained viremia. Besides viruses that are common causes of infection, metagenomics revealed the presence of several novel viruses and variants that are overlooked in clinical routine and represent potential sources of unrecognized systemic infections. Our aim was to describe the prevalence and the dynamics of 17 DNA and 3 RNA viral infections using (r(RT-)PCR) assays on plasma samples of adult allo-HSCT recipients over a one-year period after HSCT. Methods: 109 adult patients that received a first allo-HSCT from 1st March 2017 to 31st January 2019 we included in this longitudinal observational monocentric cohort study. 17 DNA and 3 RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays performed on plasma samples collected at five time-points (day 0 and 30 days, 3 months, 6 months and one year after HSCT). Results: TTV was the most prevalent with an increasing prevalence to 96% of patients at 3 months. HPgV-1 prevalence ranged from 26 to 36% of patients. TTV and HPgV-1 plasma viral load peaked at month 3 (TTV: median 3.29E5 copies/ml [range, 3.37E2 to 4.06E9 copies/ml]; HPgV-1: median 1.18E6 copies/ml [range, 2.61E3 to 4.49E7 copies/ml]). Among Polyomaviridae, BKPyV, JCPyV, MCPyV, HPyV6 and 7 were detected in ≥10% of patients at ≥1 time-point. HPyV6 and HPyV7 prevalence reached 27% and 12% of patients at month 3. Among those, 41% and 63% had quantifiable viral loads, with median viral loads above 1E3copies/ml and results may suggest HPyV6 sustained viremia. Co-detections were frequent, in particular at 3 months with ≥2 viruses detected in 72% of patients. Conclusion: Our study confirms that TTV and HPgV-1 infections are highly prevalent and that infection may be sustained up to one year after allo-HSCT. Our systematic and large strategy of screening also revealed diverse and numerous co-detections, and that several novel Polyomaviridae (MCPyV, HPyV6/7) that are overlooked in clinical routine are as or more frequently detected compared to classical culprits. Our results underscores the need for further studies investigating the clinical impact of classical culprits together with other viruses in particular novel Polyomaviridae and HPgV-1.

opencc-by-4.0Mar 2022View details →

The EGFR signaling modulates in mesenchymal stem cells the expression of miRNAs involved in the interaction with breast cancer cells

We previously demonstrated that the epidermal growth factor receptor (EGFR) modulates in mesenchymal stem cells (MSCs) the expression of a number of genes coding for secreted proteins that promote breast cancer progression. However, the role of the EGFR in modulating in MSCs the expression of miRNAs potentially involved in the progression of breast cancer remains largely unexplored. Following small RNA-sequencing, we identified 36 miRNAs differentially expressed between MSCs untreated or treated with the EGFR ligand transforming growth factor α (TGFα), with a fold change (FC) <0.56 or FC ≥1.90 (CI, 95%). KEGG analysis revealed a significant enrichment in signaling pathways involved in cancer development and progression. EGFR activation in MSCs downregulated the expression of different miRNAs, including miR-23c. EGFR signaling also reduced the secretion of miR-23c in conditioned medium from MSCs. Functional assays demonstrated that miR-23c acts as tumor suppressor in basal/claudin-low MDA-MB-231 and MDA-MB-468 cells, through the repression of IL-6R. MiR-23c downregulation promoted cell proliferation, migration and invasion of these breast cancer cell lines. Collectively, our data suggested that the EGFR signaling regulates in MSCs the expression of miRNAs that might be involved in breast cancer progression, providing novel information on the mechanisms that regulate the MSC-tumor cell cross-talk.We previously demonstrated that the epidermal growth factor receptor (EGFR) modulates in mesenchymal stem cells (MSCs) the expression of a number of genes coding for secreted proteins that promote breast cancer progression. However, the role of the EGFR in modulating in MSCs the expression of miRNAs potentially involved in the progression of breast cancer remains largely unexplored. Following small RNA-sequencing, we identified 36 miRNAs differentially expressed between MSCs untreated or treated with the EGFR ligand transforming growth factor α (TGFα), with a fold change (FC) <0.56 or FC ≥1.90 (CI, 95%). KEGG analysis revealed a significant enrichment in signaling pathways involved in cancer development and progression. EGFR activation in MSCs downregulated the expression of different miRNAs, including miR-23c. EGFR signaling also reduced the secretion of miR-23c in conditioned medium from MSCs. Functional assays demonstrated that miR-23c acts as tumor suppressor in basal/claudin-low MDA-MB-231 and MDA-MB-468 cells, through the repression of IL-6R. MiR-23c downregulation promoted cell proliferation, migration and invasion of these breast cancer cell lines. Collectively, our data suggested that the EGFR signaling regulates in MSCs the expression of miRNAs that might be involved in breast cancer progression, providing novel information on the mechanisms that regulate the MSC-tumor cell cross-talk.

dryad36/100

The PLOD2/Succinate axis regulates the epithelial-mesenchymal plasticity and cancer cell stemness

Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics (SIRM) analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including the elevation of cytoplasmic succinate levels. Treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation (ChIP) and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) was associated with an elevation of cytoplasmic succinate during the EMT process. Silence of PLOD2 expression in breast cancer cells reduced succinate levels and inhibited cancer cell mesenchymal phenotypes and stemness, which was accompanied by elevated 5hmC levels in chromatin. Importantly, exogenous succinate rescued cancer cell stemness and 5hmC levels in PLOD2-silenced cells, suggesting that PLOD2 promotes cancer progression at least partially through succinate. These results reveal the previously unidentified function of succinate in enhancing cancer cell plasticity and stemness.

opencc-zeroMar 2023View details →

Lattice kinetic Monte Carlo model to simulate RNA polymerase II clusters during stem cell differentiation

This data set includes Python scripts (numerical simulation and analysis) and already generated simulation data for RNA polymerase II clusters during stem cell differentiation. It includes the whole data to recreate panels.

Microscopy-based assessment of RNA polymerase II clusters during differentiation of cultured mouse embryonic stem cells

This repository contains the data and MatLab analysis scripts of the analysis of RNA polymerase II clusters over the course of differentiation of cultured mouse embryonic stem cells (mESCs). The cells were induced towards differentiation by either withdrawal of lineage-inhibiting factors (-LIF) or by RHB treatment. Both treatments were carried out in duplicate in independent experiments. Time course data were obtained by collection of cells at 3, 6, 12, 24, and 48 hours following the beginning of induction. Control data from unindexed cells were obtained at 24 and 48 hours. Cells were cultured, treated, collected, and fixed at University Medical Center Göttingen by Yomna Gohar, Priya Kumar, and Carmelo Ferrai. Fixed cells were fluorescently labeled and microscopy images were recorded and analyzed at Karlsruhe Institute of Technology by Lennart Hilbert.  To analyse date data, the raw image data are first extracted into MatLab-native files using the <a href="https://zenodo.org/api/files/2f2192f4-a05c-4969-ba0a-4f235b837709/MultiPosition_extraction_nd2.m">MultiPosition_extraction_nd2.m</a> script. The actual analysis is then carried out using the <a href="https://zenodo.org/api/files/2f2192f4-a05c-4969-ba0a-4f235b837709/ClusterAnalysis.m">ClusterAnalysis.m</a> script. Example microscopy images were produced using the <a href="https://zenodo.org/api/files/2f2192f4-a05c-4969-ba0a-4f235b837709/ExampleImages.m">ExampleImages.m</a> script. The extracted data can be reviewed using the <a href="https://zenodo.org/api/files/2f2192f4-a05c-4969-ba0a-4f235b837709/ReviewExtractedStacks.m">ReviewExtractedStacks.m</a> script. This is the main repository, containing the image analysis scripts alongside the links to the raw image data used in the analysis. The raw data are too large to be stored within this single repository, and therefore can be found at the following additional addresses. Differentiation by withdrawal of lineage-inhibiting factors (-LIF): <a href="https://doi.org/10.5281/zenodo.8013281">10.5281/zenodo.8013281</a> Differentiation with addition of RHB for neuronal fate induction (RHB): <a href="https://doi.org/10.5281/zenodo.8013307">10.5281/zenodo.8013307</a>

opencc-by-3.0-usApr 2023View details →

Rational Modification of Human Gut Microbial Metabolites by Dietary Resistant Starch in Patients After Allogeneic Hematopoietic Stem Cell Transplantation: A Prospective Feasibility Study

We conducted a prospective longitudinal feasibility study in patients undergoing allo-HCT for hematological malignancies to test the hypothesis that defined and consistent administration of resistant starch will rationally modify intestinal microbiota dependent metabolites, particularly the short chain fatty acids (SCFA), such as butyrate.  Ten adults undergoing human leukocyte antigen-matched, related-donor myeloablative allo-HCT were enrolled and received resistant potato starch (RPS) daily from day -7 to day 100 after allo-HCT.

Single cell analysis of human mesenchymal stem cells

This dataset including the RDS files, including meta data, labeled assays, and reduction map information in order to ensure the reproducibility of the scRNA-seq data of human MSCs. The research "Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1" has been published on Nature Communications (https://doi.org/10.1038/s41467-023-39958-5).

[Data S10] Microbiota dictate T cell clonal selection to promote graft-vs-host disease after stem cell transplantation

Data S10. 10x genomics sequencing data files for Figure 5. Matrix file "sample_filtered_feature_bc_matrix.h5" and V(D)J annotations "filtered_contig_annotations.csv" are included below. Accompanying code can be found at https://github.com/acyeh-lab/2023/tree/main/scseq.

opencc-by-4.0Feb 2023View details →

A Single-cell Perturbation Landscape of Colonic Stem Cell Polarisation

Cancer cells are regulated by oncogenic mutations and microenvironmental signals, yet these processes are often studied separately. To functionally map how cell-intrinsic and cell-extrinsic cues co-regulate cell-fate in colorectal cancer (CRC), we performed a systematic single-cell analysis of 1,107 colonic organoid cultures regulated by 1) CRC oncogenic mutations, 2) microenvironmental fibroblasts and macrophages, 3) stromal ligands, and 4) signalling inhibitors. Multiplexed single-cell analysis revealed a stepwise epithelial differentiation landscape dictated by combinations of oncogenes and stromal ligands, spanning from fibroblast-induced Clusterin (CLU)+ revival colonic stem cells (revCSC) to oncogene-driven LRIG1+ hyper-proliferative CSC (proCSC). The transition from revCSC to proCSC is regulated by decreasing WNT3A and TGF-β-driven YAP signalling and increasing KRASG12D or stromal EGF/Epiregulin-activated MAPK/PI3K flux. We find APC-loss and KRASG12D collaboratively limit access to revCSC and disrupt stromal-epithelial communication -- trapping epithelia in the proCSC fate. These results reveal that oncogenic mutations dominate homeostatic differentiation by obstructing cell-extrinsic regulation of cell-fate plasticity.

Pregnancy-Responsive Pools of Adult Neural Stem Cells For Transient Neurogenesis in Mothers

These are the RDS objects of the resulting files from our analyses, converted to Spatial Experiment object. These files can be loaded into spatialLIBD directly to allow interactive exploration of the data locally. In the new version of the dataset, we included the high resolution .tiff images of all of the samples. Furthermore, we included the low resolution (lowres) output from the spaceranger for the researchers who want to use these files. Higher resolution images (hires) were previously shared in the GEO submission alongside the raw sequencing data.