Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators - Cell Stem Cell. 2016 Oct 6Eicosanoids / G-CSF / Mobilization / Transplantation
Physiological stem cell function is regulated by secreted factors produced by niche cells. In this study, we describe an unbiased approach based on the differential single-cell gene expression analysis of mesenchymal osteolineage cells close to, and further removed from, hematopoietic stem/progenitor cells (HSPCs) to identify candidate niche factors. Mesenchymal cells displayed distinct molecular profiles based on their relative location. We functionally examined, among the genes that were preferentially expressed in proximal cells, three secreted or cell-surface molecules not previously connected to HSPC biology-the secreted RNase angiogenin, the cytokine IL18, and the adhesion molecule Embigin-and discovered that all of these factors are HSPC quiescence regulators. Therefore, our proximity-based differential single-cell approach reveals molecular heterogeneity within niche cells and can be used to identify novel extrinsic stem/progenitor cell regulators. Similar approaches could also be applied to other stem cell/niche pairs to advance the understanding of microenvironmental regulation of stem cell function.
Silberstein L1, Goncalves KA2, Kharchenko PV3, Turcotte R4, Kfoury Y1, Mercier F1, Baryawno N1, Severe N1, Bachand J1, Spencer JA1, Papazian A1, Lee D1, Chitteti BR5, Srour EF5, Hoggatt J1, Tate T1, Lo Celso C6, Ono N7, Nutt S8, Heino J9, Sipilä K9, Shioda T10, Osawa M11, Lin CP4, Hu GF12, Scadden DT13.