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Adult Neural Stem Cells Are Alerted by Systemic Inflammation through TNF-α Receptor Signaling

2020; Elsevier BV; Volume: 28; Issue: 2 Linguagem: Inglês

10.1016/j.stem.2020.10.016

1934-5909

Germán Belenguer, Pere Duart-Abadía, Antonio Jordán‐Pla, Ana Domingo-Muelas, Laura Blasco-Chamarro, Sacri R. Ferrón, José Manuel Morante‐Redolat, Isabel Fariñas,

Pluripotent Stem Cells Research

Adult stem cells (SCs) transit between the cell cycle and a poorly defined quiescent state. Single neural SCs (NSCs) with quiescent, primed-for-activation, and activated cell transcriptomes have been obtained from the subependymal zone (SEZ), but the functional regulation of these states under homeostasis is not understood. Here, we develop a multilevel strategy to analyze these NSC states with the aim to uncover signals that regulate their level of quiescence/activation. We show that transitions between states occur in vivo and that activated and primed, but not quiescent, states can be captured and studied in culture. We also show that peripherally induced inflammation promotes a transient activation of primed NSCs (pNSCs) mediated by tumor necrosis factor α (TNF-α) acting through its receptor, TNF receptor 2 (TNFR2), and a return to quiescence in a TNF receptor 1 (TNFR1)-dependent manner. Our data identify a signaling pathway promoting NSC alertness and add to the emerging concept that SCs can respond to the systemic milieu.