that were programmed via viral gene manipulation to signal through the notch and angiopoietin pathways were found to support and maintain lt-hscs. despite the difficulty in isolating sinusoidal ecs, experimental evidence suggests that these cells may play a role in regulating hscs. current research suggests that adipocytes in the bone marrow negatively regulate hsc activity. hscs isolated from adipocyte-rich vertebrae displayed decreased activity. in addition, isolation of adipocyte-containing stromal cells have shown adipocyte inhibition of the ability of hscs to proliferate and form hematopoietic colonies. finally, leukocytes may influence hscs directly or indirectly. for instance, b lymphocytes influence above stromal cells via the neurotransmitter acetylcholine. dysregulation cancer of the many transcriptional regulators of hematopoiesis, nearly all induce leukemia when aberrant. chromosomal translocation is a hallmark of leukemia, and tal1-induced translocation deregulates expression at the locus, while runx1-induced translocation results in chimeric fusion proteins. these chimeric transcription factors can result in the improper repression or activation of the target gene, as well as the inappropriate recruitment of chromatin-modifying enzymes. pax5 and notch mutations can result in b-cell and t-cell leukemias, respectively. dysregulation of stromal cells can in some cases induce genetic lesions in hematopoietic compartment; for example, mutations in the osteoblastic lineage cells resulted in malignant hematopoiesis. osteoblasts may also be dysregulated by the presence of solid tumors (outside the bone marrow); one study showed that mouse lung tumors increased osteoblast activity and numbers and that these cells were important to the outgrowth of the tumor in the lung via the production of tumor-infiltrating neutrophils. cardiovascular disease the hematopoietic niche is affected by cardiovascular disease, as the relative frequencies of stromal niche cells as well as their phenotypes are changing. these alterations depend on the specific condition and trigger changes in blood cell production. diabetes influences bone marrow endothelium, which may alter myeloid leukocyte generation. this may be relevant for diabetes-associated morbidities such as atherosclerosis. hypertension and atherosclerosis trigger endothelial dysfunction and myocardial infarction induces angiogenesis in the bone marrow. inflammation osteoblasts may be involved in other inflammatory systemic diseases, which is supported by studies using mouse models of sepsis. mesenchymal cells' response to β-adrenergic stimulation is altered in diabetes, which impairs g-csf-induced hscp mobilization.