Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA189033 | ENA |
REPOSITORIES: ENA
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Project description:Molecular analysis of the subaortic hematopoietic stem cell niche
| PRJNA669831 | ENA
Project description:We report an approach biased only by the anatomic proximity of hematopoietic stem/progenitor cells (HSPC) to a putative niche cell as the criterion for molecular analysis. Comparative RNA-Seq profiling of single mesenchymal cells immediately proximal to transplanted HSPCs and those located further away revealed that HSPC-proximal cells have a distinct genome-wide transcriptional signature, highly enriched for genes previously implicated in HSPC niche function.
2016-07-13 | GSE52359 | GEO
Project description:Molecular analysis of the subaortic hematopoietic stem cell niche [E12.5]
| PRJNA670008 | ENA
Project description:Molecular analysis of the subaortic hematopoietic stem cell niche [E11.5]
| PRJNA670009 | ENA
Project description:Molecular analysis of the subaortic hematopoietic stem cell niche [E10.5_2]
| PRJNA670010 | ENA
Project description:Molecular analysis of the subaortic hematopoietic stem cell niche [E10.5_1]
| PRJNA670012 | ENA
Project description:Maintenance of hematopoietic stem cell (HSC) function in the niche is an orchestrated event. Osteomacs (OM), are key cellular components of the niche. Previously, we documented that osteoblasts, OM, and megakaryocytes interact to promote hematopoiesis. Here, we further characterize OM and identify megakaryocyte-induced mediators that augment the role of OM in the niche. Single cell mRNAseq, mass spectrometry, and CyTOF examination of megakaryocyte-stimulated OM suggested that upregulation of CD166 and Embigin on OM augment their hematopoiesis maintenance function. CD166 knockout OM or shRNA-Embigin knockdown OM, confirmed that loss of these molecules significantly reduced OM ability to augment the osteoblast-mediated hematopoietic enhancing activity. Recombinant CD166 and Embigin partially substituted for OM function, characterizing both proteins as critical mediators of OM hematopoietic function. Our data identify Embigin and CD166 as OM-regulated critical components of HSC function in the niche and potential participants in various in vitro manipulations of stem cells.
2024-01-11 | MSV000093840 | MassIVE
Project description:Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms with defects in hematopoietic stem/progenitor cells (HSPCs) and possibly the HSPC niche. Here we show that patient-derived mesenchymal stromal cells (MDS MSCs) display a disturbed differentiation program and are essential for the propagation of MDS-initiating lin-CD34+CD38- stem cells in orthotopic xenografts. Overproduction of niche factors such as N-Cadherin, IGFBP2, VEGFA and LIF is associated with the ability of MDS MSCs to enhance MDS expansion. These factors represent putative therapeutic targets to disrupt critical hematopoietic-stromal interactions in MDS. Finally, healthy MSCs adopt "MDS-MSC like" molecular features when exposed to hematopoietic MDS cells, indicative of an instructive remodeling of their microenvironment. This patient-derived xenograft model therefore provides functional and molecular evidence that MDS is a complex disease involving both the hematopoietic and stromal compartments. The resulting deregulated expression of niche factors may well also be a feature of other hematopoietic malignancies.
| EGAS00001000716 | EGA
Project description:Mead BE, Ordovas-Montanes J, Braun AP, Levy LE, Bhargava P, Szucs MJ, Ammendolia DA, MacMullan MA, Zheng Y, Yin X, Hughes TK, Wadsworth MH, Ahmad R, Rakoff-Nahoum S, Carr SA, Langer R, Collins JJ, Shalek AK, Karp JM. BMC Biology 2018.
Background: Single-cell genomic methods now provide unprecedented resolution for characterizing the component cell types and states of tissues, such as the epithelial subsets of the gastrointestinal tract. Nevertheless, functional studies of these subsets at scale require faithful in vitro models of identified in vivo biology. While intestinal organoids have been invaluable in providing mechanistic insights in vitro, the extent to which organoid-derived cell types recapitulate their in vivo counterparts remains formally untested, with no systematic approach for improving model fidelity.
Results: Here, we present a generally applicable framework that utilizes massively-parallel single-cell RNA-seq to compare cell types and states found in vivo to those of in vitro models, such as organoids. Furthermore, we leverage identified discrepancies to improve model fidelity. Using the Paneth cell (PC), which supports the stem cell niche and produces the largest diversity of antimicrobials in the small intestine, as an exemplar, we uncover fundamental gene expression differences in lineage-defining genes between in vivo PCs and those of the current in vitro organoid model. With this information, we nominate a molecular intervention to rationally improve the physiological fidelity of our in vitro PCs. We then perform transcriptomic, cytometric, morphologic, and proteomic characterization, and demonstrate functional (antimicrobial activity, niche support) improvements in Paneth cell physiology.
Conclusions: Our systematic approach provides a simple workflow for identifying the limitations of in vitro models and enhancing their physiological fidelity. Using adult stem cell-derived PCs within intestinal organoids as a model system, we successfully benchmark organoid representation relative to in vivo of a specialized cell type and use this comparison to generate a functionally improved in vitro PC population. We predict that the generation of rationally-improved cellular models will facilitate mechanistic exploration of specific disease-associated genes in their respective cell types.
2017-07-20 | MSV000081369 | MassIVE
Project description:Generation of abundant engraftable hematopoietic cells from autologous tissues promises new therapies for hematologic diseases. Differentiation of pluripotent stem cells into hematopoietic cells results in emergence of cells that have poor engraftment potential. To circumvent this hurdle, we have devised a vascular niche model to phenocopy the developmental microenvironment of hemogenic cells thereby enabling direct transcriptional reprogramming of human endothelial cells (ECs) into hematopoietic cells. In this approach, transduction of human umbilical vein ECs (HUVECs) or adult human dermal microvascular ECs (hDMECs) with transcription factors (TFs), FOSB, GFI1, RUNX1, and SPI1 (FGRS) and induction with a instructive vascular niche feeder layer in a xenobiotic- and serum-free microenvironment results in generation of long-term engraftable hematopoietic multilineage progenitors (rEC-HMLPs). The rEC-HMLPs had robust proliferative and multilineage colony forming units (CFU) potential, including granulocytic/monocytic, megakaryocytic, erythroid and lymphoid lineages. When transplanted, hDMEC-derived rEC-HMLPs were capable of long-term multilineage primary and secondary hematopoietic engraftment. A subset of engrafted rEC-HMLPs phenotypically and functionally resembled cord blood cells. By conditionally expressing the FGRS TFs, we further optimized reprogramming of ECs into rEC-HMLPs manifesting features of self-renewing multi-potent progenitor populations (MPPs). Our approach replicates critical aspects of hematopoietic development and essential role of vascular niche induction in orchestrating hematopoietic specification and may prove useful for engineering autologous engraftable hematopoietic cells for treatment of inherited and acquired blood disorders. . Transcriptome sequencing of rEC-HMLPs, hDMECs, HUVECs and other cell types
2014-07-11 | E-GEOD-57662 | biostudies-arrayexpress