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:Purpose: To investigate whether the skeletal retardation observed in NG2-cre/Pot1afl/fl mice affected hematopoiesis. Methods: Whole bone marrow cells mRNA profiles of 2-week-old wild-type (NG2-cre/Pot1awt/wt) and Pot1a knockout (NG2-cre/Pot1afl/fl) mice were generated by deep sequencing, using Illumina NextSeq 500. Results: We compared the relative sizes of these subpopulations between the NG2-cre/Pot1afl/fl and control mice and found a significant reduction in cells of the B-cell lineage in NG2-cre/Pot1afl/fl marrow. Cell subpopulations associated with B-cell differentiation from hematopoietic stem/progenitor cells (HSPCs) were identified according to the expression of established marker genes. Conclusions: Bone marrow microenvironments composed of POT1a-deleted MSPCs impair B-cell development.
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:We identified the genes regulated by hindlimb ischemia in leukocytes and hematopoietic stem and progenitor cells isolated from the bone marrow in mice. We selected some of these genes based on their expression and further evaluated their functions using a wise array of techniques.
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:Regulation of hematopoietic stem cells (HSCs) by bone marrow (BM) niches has been extensively studied; however, whether and how HSC subpopulations are distinctively regulated by BM niches remain unclear. Here, we functionally distinguished reserve HSCs (rHSCs) from primed HSCs (pHSCs) based on their response to chemotherapy and examined how they are dichotomously regulated by BM niches. Both pHSCs and rHSCs supported long-term hematopoiesis in homeostasis; however, pHSCs were sensitive but rHSCs were resistant to chemotherapy. Surviving rHSCs restored the HSC pool and supported hematopoietic regeneration after chemotherapy. The rHSCs were preferentially maintained in the endosteal region that enriches N-cadherin+ (Ncad+) bone-lining cells in homeostasis and post-chemotherapy. N-cad+ cells were functional bone and marrow stromal progenitor cells (BMSPCs), giving rise to osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Finally, ablation of Ncad+ niche cells or deletion of SCF from N-cad+ niche cells impaired rHSC maintenance during homeostasis and regeneration.