Model of HSC Activation Cycle

<div><p>(A) Normal HSCs reside in a quiescent niche in a “state of readiness” exemplified by the indicated genes.</p> <p>(B) Upon stress (5FU treatment), HSCs “pause” by remaining quiescent and in their niche while they “prepare” to proliferate. HSCs receive signals from proinflammatory cytokines at this point. The signals induce a proliferative state that is divisible into early (C) and late (D) phases.</p> <p>(C) “Early proliferation” is marked by an increase in expression of genes involved in DNA replication, repair, and cell migration molecules that allow movement of HSCs from the quiescence niche to the proliferative zone.</p> <p>(D) “Late proliferation” is marked by expression of many cell cycle genes as well as many energy pathway molecules.</p> <p>(E) Re-induction of quiescence involves changes in migratory molecule expression, which leads to return of cells to their quiescence niche, as well the expression of antiproliferative genes.</p></div

Gene Expression Profiles Correlate with Protein Expression on HSCs

<div><p>(A) Gene expression over time. The actual observed values of each replicate at each time point are shown in red, and the line connects the predicted expression value at each time point based on our regression analysis.</p> <p>(B) Antigen expression on HSCs measured by flow cytometry. Gray lines represent negative control, red lines represent protein expression at day 0, and blue lines represent protein expression at day 7.</p> <p>(C) Cell cycle analysis of CD48⁻ and CD48⁺ HSCs isolated 6 d post 5FU treatment.</p></div