Similar Datasets
Project description:The advent of single cell (Sc) genomics has challenged the dogma of haematopoiesis as a tree-like structure of stepwise lineage commitment through distinct and increasingly restricted progenitor populations. Instead, analysis of ScRNA-seq has proposed that the earliest events in human hematopoietic stem cell (HSC) differentiation are characterized by only subtle molecular changes, with hematopoietic stem and progenitor cells (HSPCs) existing as a continuum of low-primed cell-states that gradually transition into a specific lineage (CLOUD-HSPCs). Here, we combine ScRNA-seq, ScATAC-seq and cell surface proteomics to dissect the heterogeneity of CLOUD-HSPCs at different stages of human life. Within CLOUD-HSPCs, pseudotime ordering of both mRNA and chromatin data revealed a bifurcation of megakaryocyte/erythroid and lympho/myeloid trajectories immediately downstream a subpopulation with an HSC-specific enhancer signature. Importantly, both HSCs and lineage-restricted progenitor populations could be prospectively isolated based on correlation of their molecular signatures with CD35 and CD11A expression, respectively. Moreover, we describe the changes that occur in this heterogeneity as hematopoiesis develops from neonatal to aged bone marrow, including an increase of HSCs and depletion of lympho-myeloid biased MPPs. Thus, this study dissects the heterogeneity of human CLOUD-HSPCs revealing distinct HSPC-states of relevance in homeostatic settings such as ageing.
2023-09-27 | GSE173076 | GEO
Project description:The advent of single cell (Sc) genomics has challenged the dogma of haematopoiesis as a tree-like structure of stepwise lineage commitment through distinct and increasingly restricted progenitor populations. Instead, analysis of ScRNA-seq has proposed that the earliest events in human hematopoietic stem cell (HSC) differentiation are characterized by only subtle molecular changes, with hematopoietic stem and progenitor cells (HSPCs) existing as a continuum of low-primed cell-states that gradually transition into a specific lineage (CLOUD-HSPCs). Here, we combine ScRNA-seq, ScATAC-seq and cell surface proteomics to dissect the heterogeneity of CLOUD-HSPCs at different stages of human life. Within CLOUD-HSPCs, pseudotime ordering of both mRNA and chromatin data revealed a bifurcation of megakaryocyte/erythroid and lympho/myeloid trajectories immediately downstream a subpopulation with an HSC-specific enhancer signature. Importantly, both HSCs and lineage-restricted progenitor populations could be prospectively isolated based on correlation of their molecular signatures with CD35 and CD11A expression, respectively. Moreover, we describe the changes that occur in this heterogeneity as hematopoiesis develops from neonatal to aged bone marrow, including an increase of HSCs and depletion of lympho-myeloid biased MPPs. Thus, this study dissects the heterogeneity of human CLOUD-HSPCs revealing distinct HSPC-states of relevance in homeostatic settings such as ageing.
2023-09-27 | GSE173075 | GEO
Project description:Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy
| PRJNA723746 | ENA
Project description:Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy [CITE-seq]
| PRJNA723753 | ENA
Project description:Single-Cell Multiomics Reveals Distinct Cell States at the Top of the Human Hematopoietic Hierarchy [scATAC-seq]
| PRJNA723752 | ENA
Project description:One of the keys to achieving skin regeneration lies within understanding the heterogeneity of neonatal fibroblasts, which support skin regeneration. However, the molecular underpinnings regulating the cellular states and fates of these cells are not fully understood. To investigate this, we performed a parallel multiomics analysis by processing neonatal murine skin for single-cell Assay for Transposase-Accessible Chromatin sequencing and single-cell RNA sequencing separately. Our approach revealed that fibroblast clusters could be sorted into papillary and reticular lineages on the basis of transcriptome profiling, as previously reported. However, single-cell Assay for Transposase-Accessible Chromatin sequencing analysis of neonatal fibroblast lineage markers, such as Dpp4/Cd26, Corin, and Dlk1 along with markers of myofibroblasts, revealed accessible chromatin in all fibroblast populations despite their lineage-specific transcriptome profiles. These results suggest that accessible chromatin does not always translate to gene expression and that many fibroblast lineage markers reflect a fibroblast state, which includes neonatal papillary fibroblasts, reticular fibroblasts, and myofibroblasts. This analysis also provides a possible explanation as to why these marker genes can be promiscuously expressed in different fibroblast populations under different conditions. Our single-cell Assay for Transposase-Accessible Chromatin sequencing analysis also revealed that the functional lineage restriction between dermal papilla and adipocyte fates is regulated by distinct chromatin landscapes. Finally, we have developed a webtool for our multiomics analysis: https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/.
| S-EPMC9203604 | biostudies-literature
Project description:A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that elicited them.
| S-EPMC4687963 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is the most common liver cancer with a high rate of metastasis. However, the molecular mechanisms that drive metastasis remain unclear. We combined single-cell transcriptomic, proteomic, and chromatin accessibility data to investigate how heterogeneous phenotypes contribute to metastatic potential in five HCC cell lines. We confirmed that the prevalence of a mesenchymal state and levels of cell proliferation are linked to the metastatic potential. We also identified a rare hypoxic subtype that has a higher capacity for glycolysis and exhibits dormant, invasive, and malignant characteristics. This subtype has increased metastatic potential. We further identified a robust 14-gene panel representing this hypoxia signature and this hypoxia signature could serve as a prognostic index. Our data provide a valuable data resource, facilitate a deeper understanding of metastatic mechanisms, and may help diagnosis of metastatic potential in individual patients, thus supporting personalized medicine.
| S-EPMC8850337 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-11 | GSE260995 | GEO
Project description:Cancer cells frequently exhibit chromosomal abnormalities. Specific cytogenetic aberrations often are predictors of outcome, especially in hematologic neoplasms, such as monosomy 7 in myeloid malignancies. The functional consequences of aneuploidy at the cellular level are difficult to assess because of a lack of convenient markers to distinguish abnormal from diploid cells. We performed single-cell RNA sequencing (scRNA-seq) to study hematopoietic stem and progenitor cells from the bone marrow of 4 healthy donors and 5 patients with bone marrow failure and chromosome gain or loss. In total, transcriptome sequences were obtained from 391 control cells and 588 cells from patients. We characterized normal hematopoiesis as binary differentiation from stem cells to erythroid and myeloid-lymphoid pathways. Aneuploid cells were distinguished from diploid cells in patient samples by computational analyses of read fractions and gene expression of individual chromosomes. We confirmed assignment of aneuploidy to individual cells quantitatively, by copy-number variation, and qualitatively, by loss of heterozygosity. When we projected patients' single cells onto the map of normal hematopoiesis, diverse patterns were observed, broadly reflecting clinical phenotypes. Patients' monosomy 7 cells showed downregulation of genes involved in immune response and DNA damage checkpoint and apoptosis pathways, which may contribute to the clonal expansion of monosomy 7 cells with accumulated gene mutations. scRNA-seq is a powerful technique through which to infer the functional consequences of chromosome gain and loss and explore gene targets for directed therapy.
| S-EPMC5746166 | biostudies-literature