A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators
Tekijät: Silberstein L, Goncalves KA, Kharchenko PV, Turcotte R, Kfoury Y, Mercier F, Baryawno N, Severe N, Bachand J, Spencer JA, Papazian A, Lee D, Chitteti BR, Srour EF, Hoggatt J, Tate T, Lo Celso C, Ono N, Nutt S, Heino J, Sipila K, Shioda T, Osawa M, Lin CP, Hu GF, Scadden DT
Kustantaja: CELL PRESS
Julkaisuvuosi: 2016
Journal: Cell Stem Cell
Tietokannassa oleva lehden nimi: Cell Stem Cell
Lehden akronyymi: CELL STEM CELL
Vuosikerta: 19
Numero: 4
Aloitussivu: 530
Lopetussivu: 543
Sivujen määrä: 14
ISSN: 1934-5909
eISSN: 1875-9777
DOI: https://doi.org/10.1016/j.stem.2016.07.004
Tiivistelmä
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.
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.
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