Table 1.

The influences and mechanisms of a CVD-promoting lifestyle on HSC homeostasis.

Lifestyle	Influences on BM HSCs	Potential Mechanisms	Species
Psychosocial stress	Proliferation; Mobilization; Myeloid-biased differentiation.	Noradrenaline released by SNS signals niche cells via β-AR signaling to disrupt CXCL12-CXCR4 axis [48,49,50]; dopamine released by SNS activates PKA-Lck-ERK axis in HSCs via D2-type receptor [51]; glucocorticoids released by HPA axis upregulate actin-organizing molecules in HSCs via NR3C1 [21]; decrease in CXCL12 expression in niche cells [52].	Mouse
Sleep problems	Proliferation; Myeloid-biased differentiation; Pro-inflammatory priming; Mobilization?	Less production of hypocretin by hypothalamus promotes CSF1 production by BM pre-neutrophils [53]; brain PGD2 elevation and efflux induce systemic inflammation via DP1 [54]; epigenetic reprogramming and promotion of clonal hematopoiesis through accelerated genetic drift in HSCs [55]; disruption of circadian rhythm leading to deregulated SNS activation [56,57,58], serum proteolytic cascades [59,60,61], and HSC inflammasome signaling [62,63]?	Mouse Human
High-cholesterol diet	Proliferation; Expansion; Mobilization; Myeloid-biased differentiation; Pro-inflammatory priming.	Epigenetic reprogramming in HSCs [64]? SREBP2 activation-mediated Notch upregulation in HSCs [65]; SLC38A9-mTOR axis activation in HSCs [10]; promotion of clonal hematopoiesis through expediting somatic evolution in HSCs [47]; elevated serum levels of CSF3 due to IL-23 generation by splenic dendritic cells and macrophages and decreased CXCL12 production by MSCs [66]; 27-hydroxycholesterol downregulates CXCR4 on HSCs via ERα [67].	Mouse Human
High-fat diet	Proliferation; Expansion; Myeloid-biased differentiation; Pro-inflammatory priming.	MyD88 activation and epigenetic reprogramming in HSCs [68]? Oxidative stress-induced GFI1 upregulation in HSCs [69]; disruption of TGF-β receptor signaling within lipid rafts of HSCs [70]; expanded BM adipocytes produce excessive DPP4 [71]; inflammation-induced clonal hematopoiesis [72]; structural changes in microbiota alters HSC niche via activation of PPARγ2 [73].	Mouse Human
High sodium intake	Mobilization? Myeloid-biased differentiation?	Increased IL-17 release by Th17 cells [74]? Perturbation of mitochondrial respiration in HSCs [75]?	Mouse
High-Pi diet	Expansion; MK/myeloid-biased differentiation.	Activation of PPIP5K2-Akt axis in HSCs [11]; Akt-mediated increase in apoptosis resistance of HSCs [76].	Mouse
Ketogenic diet	Expansion Myeloid-biased differentiation Pro-inflammatory priming	Increased circulating levels of free PA and PA-associated lipids [77]; epigenetic reprogramming in HSCs [77]?	Mouse
Alcohol consumption	Attrition Proliferation Myeloid-biased differentiation	Acetaldehyde-toxicity-induced DNA damage activates p53 to induce apoptosis [78,79,80]; remodeling of HSC niche [81].	Mouse
Tobacco smoking	Expansion Myeloid-biased differentiation	Nicotine directly acts on nicotinic acetylcholine receptors on HSCs [82]? Remodeling of HSC niche [81,83].	Mouse
Physical inactivity/ sedentary behavior	Proliferation Expansion Mobilization Myeloid-biased differentiation	More leptin is produced by increased body fat and interacts with LepR-positive BM stromal cells to decrease expression of quiescence- and retention-promoting hematopoietic niche factors [84]; epigenetic reprogramming in HSCs [84].	Mouse Human