Social Stress Mobilizes Hematopoietic Stem Cells to Establish Persistent Splenic Myelopoiesis

Abstract

SUMMARY Psychosocial stress accelerates myelopoietic production of monocytes and neutrophils that contributes to a variety of health complications ranging from atherosclerosis to anxiety. Here, we show that social stress in mice mobilizes hematopoietic stem progenitor cells (HSPCs) from the bone marrow that enter circulation, engraft into the spleen, and establish a persistent extramedullary hematopoietic depot. These splenic progenitors actively proliferate and differentiate into multiple cell types, including monocytes, neutrophils, and erythrocytes. Splenic erythropoiesis partially abrogates stress-induced anemia. Repeated injection with isoprenaline induces progenitor mobilization to the spleen, identifying a key role for β-adrenergic signaling. Moreover, protracted splenic production of CD11b+ cells persists for at least 24 days after the cessation of social stress. Thus, chronic stress establishes a persistent extramedullary hematopoietic depot that can modify a wide range of chronic disease processes and alter homeostasis of the bi-directional regulatory axis between the nervous and immune systems.

In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms

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The effects of tamoxifen on mouse behavior

“…Although tamoxifen has been used in mouse models for a long time, the effects of tamoxifen have not been researched . In the isolation model, isolation can result in hyperactivity and depression .…”

“…All the above mentioned results were in mice that were not subjected to mouse models or mutagenesis. In the literature, many experiments are designed to make mice into animal models before or after tamoxifen administration . Therefore, we designed protocols to explore whether tamoxifen could promote or prevent behavioral alterations after the mouse model.…”

Pattern of human monocyte subpopulations in health and disease

“…Monocytes are produced during homeostasis by haematopoietic stem and progenitor cells (HSPCs) in the bone marrow (steady‐state monopoiesis). Infections, inflammations, tumours and chronic psychosocial stress can lead to emergency monopoiesis and the production of new subsets of monocytes with altered functions 7,53‐55 . Under pathological conditions, monocytes can acquire inflammatory effector functions and develop regulatory properties which are essential for tissue repair.…”