Common Sources of Inflammation and Their Impact on Hematopoietic Stem Cell Biology

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CELL MAINTENANCE (D LUCAS, SECTION EDITOR)

Common Sources of Inflammation and Their Impact on Hematopoietic Stem Cell Biology Daniel Hormaechea-Agulla 1 & Duy T. Le 1,2 & Katherine Y. King 1,2 Published online: 17 August 2020 # Springer Nature Switzerland AG 2020

Abstract Purpose of Review Inflammatory signals have emerged as critical regulators of hematopoietic stem cell (HSC) function. Specifically, HSCs are highly responsive to acute changes in systemic inflammation and this influences not only their division rate but also their lineage fate. Identifying how inflammation regulates HSCs and shapes the blood system is crucial to understanding the mechanisms underpinning these processes, as well as potential links between them. Recent Findings A widening array of physiologic and pathologic processes involving heightened inflammation are now recognized to critically affect HSC biology and blood lineage production. Conditions documented to affect HSC function include not only acute and chronic infections but also autoinflammatory conditions, irradiation injury, and physiologic states such as aging and obesity. Summary Recognizing the contexts during which inflammation affects primitive hematopoiesis is essential to improving our understanding of HSC biology and informing new therapeutic interventions against maladaptive hematopoiesis that occurs during inflammatory diseases, infections, and cancer-related disorders. Keywords Hematopoiesis . Pro-inflammatory cytokines . Infectious diseases . Bone marrow . Inflammatory conditions

Introduction Hematopoietic stem cells (HSCs) are the most primitive hematopoietic population resident in the bone marrow (BM). Although a very rare population, HSCs are the foundation of the hematopoietic tree. Through self-renewal and differentiation into other progenitor populations, HSCs have the unique ability to completely regenerate the blood system after transplantation and thus have been the focus of heavy study for many decades. HSCs are also the foundation of many hematological disorders and pathologies, since any mutation that occurs in an HSC will be passed to downstream blood

lineages. Therefore, it is of critical importance to understand the myriad processes that directly or indirectly affect HSC biology. HSCs were long perceived to be a population protected from external signals, but recent overwhelming evidence has shifted that view [1••]. For instance, inflammation is now well recognized to have an important influence on HSC function [2••, 3•]. Many types of endogenous and exogenous factors, ranging from mechanical/thermal stimuli to pathogens or aging, induce local or systemic inflammation, and each of these has the potential to affect HSC activity. The aim of this review is to summarize the pro-inflammatory mediators and sources of inflammation known to affect HSC biology.

Daniel Hormaechea-Agulla and Duy T. Le contributed equally to this work. This article is part of the Topical Collection on Cell Maintenance

Pro-inflammatory Cytokines

* Katherine Y. King [email protected]