Project description:To solve the heterogeniety of human bone marrow non-hematopoietic cells, we perfomed transcriptomic profiling of bone marrow non-hematopoietic cells using scRNAseq.
Project description:Thiele2013 - Bone marrow hematopoietic cells
The model of bone marrow hematopoietic cells metabolism is derived from the community-driven global reconstruction of human metabolism (version 2.02, MODEL1109130000
).
This model is described in the article:
A community-driven global reconstruction of human metabolism.
Thiele I, et al
.
Nature Biotechnology
Abstract:
Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven,
consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared
with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using
Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic
data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically
generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will
facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
This model is hosted on BioModels Database
and identified by: MODEL1310110030
.
To cite BioModels Database, please use: BioModels Database: An enhanced,
curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer
to CC0 Public Domain Dedication
for more information.
Project description:Hematopoietic stem cells give rise to all blood lineages, can fully re-populate the bone marrow, and easily outlive the host organism. To better understand how stem cells remain fit during aging, we analyzed the proteome of hematopoietic stem and progenitor cells.
Project description:We isolated non-hematopoietic cells from fibrotic and non-fibrotic human bone marrow and perfomed scRNAseq on them. We identified 3 different stromal populations and 2 populations of hematopoietic progenitors. Our analysis revealed mesenchymal stromal cells (MSC) as pro-fibrotic cells. MSCs were functionally reprogrammed with loss of their progenitor status and acquisition of a pro-fibrotic phenotype in the fibrotic bone marrow. Additionally, stromal cells exhibited an upregulation of pro-inflammatory mediators like S100A8/A9.
Project description:The bone marrow microenvironment is key player in the regulation and maintenance of hematopoiesis and is also involved in the pathogenesis of hematologic malignancies. We investigated the effect of KrasG12D expression in the non-hematopoietic bone marrow microenvironment. Therefore, we generated chimeric mice which express oncogenic Kras only in the non-hematopoietic system. Within 6-8 weeks, these mice developed a myelodysplastic syndrome characterized by cytopenia, myeloid expansion and signs of disturbed differentiation and marked dysplasia within the myeloid lineage. Gene expression analysis of KrasG12D expressing non-hematopoietic cells of the bone marrow microenvironment revealed a significant upregulation of multiple genes and pathways including proinflammatory signaling such as upregulation of the NLRP3 inflammasome and related genes.
Project description:Human bone marrow stromal cells (BMSCs) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key BMSC functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key BMSC regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSCs, downregulated upon culture, and lower in non-CFU-F-containing CD45neg BM cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSCs. Accordingly, EGR1 overexpression markedly decreased BMSC proliferation but considerably improved hematopoietic stroma support function as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement of BMSC stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. On the other hand, EGR1 knockdown increased ROS-mediated BMSC proliferation, and clearly reduced BMSC hematopoietic stroma support potential. These findings thus show that EGR1 is a key BMSC transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to coordinate the specific functions of BMSC in their different biological contexts.
Project description:We performed fate tracing of Gli1+ cells in homeostasis. Sorted cells were subjected to scRNAseq and integrated with non-hematopoietic cells from mice with myelofibrosis induced by either ThPO- or JAK2V617F-overexpression. Gli1+tdTom+ cells largely overlap with pro-fibrotic adipogenic and osteogenic MSCs, which show a strong upregulation of ECM related transcripts. Additionally, a subgroup of Gli1+tdTom+ cells shows similarity with bone marrow SCPs.