Project description:The non-hematopoietic cell fraction of the bone marrow (BM) is classically identified as CD45– Ter119– CD31– (herein referred to as triple-negative cells or TNCs). Although TNCs are believed to contain heterogeneous stromal cell populations, they remain poorly defined. Here we show, unexpectedly, that the vast majority of TNCs (~85%) have a hematopoietic rather than mesenchymal origin. Single cell RNA-sequencing reveals erythroid and lymphoid progenitor signatures among CD51– TNCs. When cultured with BM-derived stromal cells, Ly6D+ CD44+ CD51–TNCs give rise to B-lymphoid cells, whereas Ly6D–CD44+ CD51–TNCs generate erythroid cells. In addition, CD44+ CD51– TNCs contribute to repopulate B-lymphoid and erythroid cells after transplantation in mice. The CD44+ CD51– TNC population also expands during phenylhydrazine-induced acute hemolysis or in a model of sickle cell anemia. These findings thus uncover physiologically relevant, yet unappreciated, classes of stromal-associated CD45– hematopoietic progenitors.
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:RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Scf; GFP+Cxcl12; DsRed+ bone marrow stromal cells ,2D cultured bone marrow stromal cells and 3D cultured bone marrow stromal cells. RNA sequencing data of sorted primary and 3D cocultured Lin-Sca1+C-kit+CD150+CD48+ hematopoietic stem cells from 8-12 weeks and 12-13 months old mice. RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Pdgfra+td-Tomato+ bone marrow stromal cells from young (8 wks), middle aged (12 months) and aged (22-24 months) Lepr-Cre;td-Tomato mice.
Project description:Bone marrow stromal cells are commonly defined by CD45–Ter119–CD31– (Triple-negative cells or TNCs). In this study, we show that most TNCs are not labeled by mesenchymal cell genetic labeling models but are derived from hematopoietic stem and progenitor cells. RNA-Seq analysis of TNCs reveals erythroid and lymphoid progenitor signatures among CD51– TNCs which was confirmed by in vitro culture studies with primary bone marrow stromal cells and by in vivo transplantation experiments. We also show that CD44+CD51– TNCs expands during phenylhydrazine-induced hemolytic anemia and in a mouse model of sickle cell disease. These results uncover new classes of stromal-associated hematopoietic progenitors.
Project description:We report the single cell transcriptome of CD45+ cells from the livers of bone marrow chimeric wildtype mice with NASH that had previously been transplanted with bone marrow from TREM2-deficient or wildtype littermate mice. We show that hematopoietic TREM2 deficiency is associated with alterations in the hepatic immune cell composition in the context of NASH.
Project description:Analyze and compare the gene expression profile of human bone marrow primary CD45-CD271+ and CD45-CD271- cells. The hypothesis was some genes were differentially expressed in these two populations. Results provided important information regarding the gene expression difference of these two cell populations.
Project description:Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem and cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Ebf1-deficient MSCs have reduced mesenchymal lineage potential. Ebf1 deletion in Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+CD45-CD31-Lin- (PαS) cells in the bone marrow decreased the numbers of HSPCs and myeloid cells. EBF1 in the bone marrow niche regulates a transcriptional program that determines the functional interactions with HSCs and the long-term balance between the myeloid and lymphoid cell fates.