Prospective isolation of nonhematopoietic cells of the niche and their differential molecular interactions with HSCs.

A major limitation preventing in vivo modulation of hematopoietic stem cells (HSCs) is the incomplete understanding of the cellular and molecular support of the microenvironment in regulating HSC fate decisions. Consequently, murine HSCs cannot be generated, maintained, or expanded in culture over extended periods of time. A significantly improved understanding of the bone marrow niche environment and its molecular interactions with HSCs is pivotal to overcoming this challenge. We here prospectively isolated all major nonhematopoietic cellular niche components and cross-correlate them in detail with niche cells defined by lineage marking or tracing. Compiling an extensive database of soluble and membrane-bound ligand-receptor interactions, we developed a computational method to infer potential cell-to-cell interactions based on transcriptome data of sorter-purified niche cells and hematopoietic stem and progenitor cell subpopulations. Thus, we establish a compendium of the molecular communication between defined niche components and HSCs. Our analysis suggests an important role for cytokine antagonists in the regulation of HSC functions.

Relationship between Lipoprotein(a) and Thyroid Hormones in Hypothyroid Patients.

BACKGROUND AND OBJECTIVE: Changes in plasma lipid concentrations are well known metabolic consequences of thyroid dysfunction. The alterations are most prominent in hypothyroidism which is typically associated with pronounced hypercholesterolaemia and frequently with moderate hypertriglyceridaemia. In cases of hypothyroidism, how the serum Lp(a) levels are influenced by thyroid hormone remains unknown and contradictory results on the effect of thyroid hormone on serum Lp(a) levels have been reported. There is substantial evidence to suggest that elevated serum Lp(a) levels contribute significantly to the development of CHD. The present study was designed to determine the lipoprotein(a) [Lp(a)], lipid profile and thyroid hormone levels in newly diagnosed hypothyroid patients and to find any correlation that existed between Lp(a) and other parameters. MATERIALS AND METHODS: Untreated hypothyroid (n=50) patients were included in the study. We also included 40 normal healthy subjects as controls. Lipid profile, Lp(a) and thyroid profile were estimated by using autoanalyzers. RESULTS: The results of this study showed that levels of HDL-cholesterol were significantly decreased (p<0.001), whereas those of other lipid parameters and Lp(a) levels were found to be significantly increased (p<0.001) in hypothyroid patients as compared to those in controls. Correlation study revealed a significant positive correlation between Lp(a) and TSH levels in hypothyroid patients. CONCLUSION: Our present findings indicated that hypothyroidism could be strongly associated with lipid abnormalities that enhanced the development of cardiovascular diseases. Also, Lp(a) and non-HDL-C should be estimated with other lipid parameters as a useful index for measuring the cardiac risk in hypothyroid patients. A recommended screening should be advised for any patient with thyroid dysfunction, especially hypothyroidism, to assess lipid abnormalities by using Lp(a) and non- HDL-C and he/she should treated at the earliest.