Journal article
Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators
L Silberstein, KA Goncalves, PV Kharchenko, R Turcotte, Y Kfoury, F Mercier, N Baryawno, N Severe, J Bachand, JA Spencer, A Papazian, D Lee, BR Chitteti, EF Srour, J Hoggatt, T Tate, C Lo Celso, N Ono, S Nutt, J Heino Show all
Cell Stem Cell | CELL PRESS | Published : 2016
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 Emb..
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Awarded by National Institutes of Health
Funding Acknowledgements
We are grateful to David Clapham and Long-Jun Wu for technical advice and to Jayaraj Rajagopal, Andrew Lane, and Ya-Chieh Hsu for critical reading of the manuscript. We thank Charles Dinarello for technical advice; Laura Prickett, Kathryn Folz-Donahue, and Meredith Weglarz for cell sorting; and Edward Fox at the Dana Farber Cancer Institute Microarray core for cDNA sequencing. D.T.S. is a shareholder in Fate Therapeutics and a consultant for Fate Therapeutics, Hospira, GSK, and Bone Therapeutics. L.S., P.V.K., G.H., K.A.G., and D.T.S. filed patent applications related to the findings described in the manuscript. The work was supported by fellowship awards from Leukemia and Lymphoma Research UK and Leukemia and Lymphoma Society (to L.S.); a T32 training fellowship (to J.H.); NIH grants K25AG037596 (to P.V.K.), RO1DK107784 and RO1HL096372 (to D.T.S.), R01CA105241 and R01NS065237 (to G.H.), and F31HL128127 (to K.A.G.); a Sackler Dean's Fellow award (to K.A.G.); a Sackler Families Collaborative Cancer Biology award (to K.A.G. and G.H.); a National Health and Medical Research Council of Australia fellowship (to S.N.); the Victorian State Government Operational Infrastructure Support (to S.N.); and the Australian Government NHMRC IRIIS (to S.N.).