Biology subjects

Rohde, D.

Publications and source records attributed to Rohde, D..

3 recordsLinked to original sources

bioRxiv2025

Bone marrow mesenchymal stromal cells mediate cellular inflammation in HFpEF

During the genesis of heart failure, the myocardium recruits an abundance of bone marrow-derived leukocytes, primarily monocytes, with various disease-promoting functions. Increased hematopoiesis fuels these unfavorable changes in cardiac leukocyte origin, number and phenotype. Here we examine hematopoietic niche cells, which regulate blood progenitor proliferation and systemic monocyte supply, in obese, hypertensive mice that develop heart failure with preserved ejection fraction (HFpEF). Single cell transcriptomics revealed that in HFpEF, stromal bone marrow niche cells expand and respond strongly to IFN{gamma}. Deleting the IFN{gamma} receptor in stromal cells of Prrx1CreERT2;Ifngr1fl/fl mice reduced hematopoietic progenitor proliferation and systemic monocytes in both the steady state and HFpEF and also increased the canonical hematopoietic maintenance factor CXCL12, resulting in reduced fibrosis and improved diastolic function. CD8+ T cells in adipose tissue were a major source of IFN{gamma} in mice with HFpEF; their depletion restored CXCL12 expression and lowered monocyte numbers. ScRNA-seq in mice with ischemic heart disease uncovered a diverging marrow response. These data indicate that in HFpEF, adipose tissue, bone marrow and adaptive and innate immune cells conspire to expand harmful macrophage subsets in the heart.

immunology↗

bioRxiv2021

Cerebrospinal fluid outflow through skull channels instructs cranial hematopoiesis

Interactions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues, particularly dural lymphatic vessels that allow cerebrospinal fluid outflow, facilitate intersystem communication. Here we observe that cerebrospinal fluid exits into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria usurp this perivascular route to infect the skulls hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. Because skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in cerebrospinal fluid by regional marrow has broad implications for neurological disorders. One-Sentence SummarySkull channels transport cerebrospinal fluid from the subarachnoid space to the cranial bone marrow via a perivascular route, which bacteria use during meningitis.

immunology↗

bioRxiv2019

A mouse model of recurrent myocardial infarction reports diminished emergency hematopoiesis and cardiac inflammation

Recurrent MI is common in patients with coronary artery disease and associates with high mortality. Here we developed a surgical mouse model in which two subsequent MIs affect different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex followed by the left anterior descending branch of the coronary artery. We characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac MRI. We report that a first MI induces bone marrow \"memory\" via a circulating signal, thereby affecting hematopoietic factor expression in bone marrow macrophages. This altered the organisms reaction to subsequent events. Inspite at least similar extent of injury reported by blood troponin, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. Our data suggest that hematopoietic and innate immune responses are shaped by a preceding MI.

physiology↗