Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA306426 | ENA |
REPOSITORIES: ENA
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Project description:Development of T lymphocytes in the thymus has been widely studied in mice, but our insights into human T cell development are scarce. Using a combination of single-cell techniques and functional assays, we report deep immune profiling of human T cell development, with a focus on the initial development stages of pre-lineage commitment. We identified three thymus-seeding progenitor populations that also have a counterpart in the bone marrow. We found that the human thymus physiologically supports development of monocytes, DCs, NK cells, and limited development of B lymphocytes. These insights are important to monitor and guide regenerative therapies after hematopoietic stem cell transplantation.
2022-08-01 | GSE195812 | GEO
Project description:Lympho-myeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells
| PRJNA219339 | ENA
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:Since the first description of the involvement of Notch signaling in homeostasis especially of T cells, there is great effort in research to find new target genes of Notch that are involved in T cell development in the thymus. We developed a stroma cell free system that is able to induce T cell development in vitro called the plastic thymus. Having this new tool we decided to use the gene expression technique to get an expanded and more global picture of the changes in gene expression in T cell progenitor induced by Notch signaling via DLL4-Fc. We used microarrays to detail the global programme of gene expression in developing T-cell progenitors induced by Notch signaling. T cell progenitors generated in the plastic thymus, defined as CD93 lo, c-Kit+ cells were sorted on day 5, RNA was isolated and gene expression was analyzed using Affymetrix GeneChip Mouse Gene 1.0 ST Array. PC5B7 cultured with IL7 and SCF were stimulated with 2 μg/ml plate bound DLL4-Fc and compared to cells cultured without the Notch ligand.
2013-05-31 | E-GEOD-46191 | biostudies-arrayexpress
Project description:Human T lymphogenesis includes emergence, migration and thymus-seeding of T lymphoid precursor, followed by T-lymphocytes commitment in thymus, which are largely unknown. Here, we perform single-cell RNA sequencing using cells isolated from human hemogenic/hematopoietic sites such as aorto-gonad-mesonephros (AGM), liver, and thymic primordia spanning embryonic and fetal stages. The transcriptional atlas of thymic primordia illustrates the cellular trajectory of early T-lymphocyte development. Further, thymic seeding progenitors in liver and unique T lymphoid progenitors in AGM at CS14, are first unveiled. We also reveal the stepwise-specification of thymic epithelial cells，and the potential cell-cell interactions between T-lymphocyte progenitors and stromal cells during thymus organogenesis. Our data provide new insights into T lymphogenesis, which prospectively directs the efficient regeneration of T- lymphocytes from pluripotent stem cells
2019-10-09 | GSE133341 | GEO
Project description:FLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors WT multipotent progenitors were compared with FLT3-ITD multipotent progenitors
2014-05-16 | E-GEOD-35805 | biostudies-arrayexpress
Project description:FLT3-ITDs Introduce a Myeloid Differentiation and Transformation Bias in Lympho-myeloid Multipotent Progenitors
2014-05-16 | GSE35805 | GEO
Project description:Regulation of lineage potential and transcriptional priming by Ikaros. New insight is provided into a bivalent regulation of lineage priming in the HSC and its lympho-myeloid restricted progeny the LMPP by the lymphoid lineage-determining factor Ikaros; Whereas Ikaros is responsible for the activation of a cascade of lymphoid expression programs and for the establishment of lymphoid potential from the HSC to the LMPP it is also responsible for the repression of stem cell and erythroid genetic programs that are incompatible with further lineage restrictions emanating from the LMPP Experiment Overall Design: Ikaros null versus wt
2009-04-11 | E-GEOD-15330 | biostudies-arrayexpress
Project description:Gene expression analysis of early thymic progenitors and thymus seeding progenitors
2012-02-19 | GSE29382 | GEO