| Literature DB >> 27524439 |
Lev Silberstein1, Kevin A Goncalves2, Peter V Kharchenko3, Raphael Turcotte4, Youmna Kfoury1, Francois Mercier1, Ninib Baryawno1, Nicolas Severe1, Jacqueline Bachand1, Joel A Spencer1, Ani Papazian1, Dongjun Lee1, Brahmananda Reddy Chitteti5, Edward F Srour5, Jonathan Hoggatt1, Tiffany Tate1, Cristina Lo Celso6, Noriaki Ono7, Stephen Nutt8, Jyrki Heino9, Kalle Sipilä9, Toshihiro Shioda10, Masatake Osawa11, Charles P Lin4, Guo-Fu Hu12, David T Scadden13.
Abstract
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.Entities:
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Year: 2016 PMID： 27524439 PMCID： PMC5402355 DOI： 10.1016/j.stem.2016.07.004
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633