ArticleCell stem cell2016
Proximity-Based Differential Single-Cell Analysis of the Niche to Identify Stem/Progenitor Cell Regulators.
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Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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105citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% of its field
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Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Urinary Angiogenin as a Marker for Bladder Cancer: A Meta-Analysis.BioMed research international · 2021Pooled it
- Interleukin-18 plays a dispensable role in murine and likely also human bone marrow failure.Experimental hematology · 2019Trial
- Endothelial PERK restricts lymphoid regeneration by reducing DLL4-NOTCH3 signaling at the Pre-B niche.Cell reports · 2026Article
- Angiogenin alleviates lipotoxicity-induced impairment of skin wound healing.Cellular & molecular biology letters · 2026Article
- Crosstalk between bone and vasculature within bone.Fundamental research · 2026Review
- Embigin is involved in the regulation of early mouse kidney development.Scientific reports · 2026Article
- An interpretable Graph-Regularized Optimal Transport Framework for Diagonal Single-Cell Integrative Analysis.GigaScience · 2026Article
- Hematopoietic organoids: Opportunities and challenges in modeling human hematopoiesis and diseases in vitro.Stem cell reports · 2026Review
- Damage-induced IL-18 stimulates thymic NK cells limiting endogenous tissue regeneration.Nature immunology · 2025Article
- Article
- Article
- Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.Nature aging · 2025Article
- A stromal inflammasome Ras safeguard against Myc-driven lymphomagenesis.Nature immunology · 2025Article
- Roles and regulation of tRNA-derived small RNAs in animals.Nature reviews. Molecular cell biology · 2024Review
- Osteomacs promote maintenance of murine hematopoiesis through megakaryocyte-induced upregulation of Embigin and CD166.Stem cell reports · 2024Article
- Embigin deficiency leads to delayed embryonic lung development and high neonatal mortality in mice.iScience · 2024Article
- Age-related noncanonical TRMT6-TRMT61A signaling impairs hematopoietic stem cells.Nature aging · 2024Article
- Influences on the Hematopoietic Stem Cell Niche.SciBase hematology & blood disorders · 2024Article
- The evolving hematopoietic niche during development.Frontiers in molecular biosciences · 2024Review
- Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 11 institutions in 5 countries.
Lev SilbersteinCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Kevin A GoncalvesGraduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA; Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Peter V KharchenkoHarvard Stem Cell Institute, Cambridge, MA 02138, USA; Department for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Raphael TurcotteHarvard Stem Cell Institute, Cambridge, MA 02138, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02445, USA.
Youmna KfouryCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Francois MercierCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Ninib BaryawnoCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Nicolas SevereCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Jacqueline BachandCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Joel A SpencerCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Ani PapazianCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Dongjun LeeCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Brahmananda Reddy ChittetiIndiana University, Indianapolis, IN 46202, USA.
Edward F SrourIndiana University, Indianapolis, IN 46202, USA.
Jonathan HoggattCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Tiffany TateCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Cristina Lo CelsoImperial College London, London SW7 2AZ, UK.
Noriaki OnoSchool of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
Stephen NuttWalter and Eliza Hall Research Institute, Parkville, VIC 3052, Australia.
Jyrki HeinoUniversity of Turku, Turku 20014, Finland.
Kalle SipiläUniversity of Turku, Turku 20014, Finland.
Toshihiro ShiodaCancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Masatake OsawaGifu University, Gifu 501-1193, Japan.
Charles P LinHarvard Stem Cell Institute, Cambridge, MA 02138, USA; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02445, USA.
Guo-Fu HuGraduate Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA; Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA. Electronic address: guo-fu.hu@tufts.edu.
David T ScaddenCenter for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02445, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: david_scadden@harvard.edu.
Harvard Stem Cell Institute · USHarvard University · USMassachusetts General Hospital · USIndiana University – Purdue University Indianapolis · USUniversity of Turku · FIGifu University · JPImperial College London · GBTufts Medical Center · USTufts University · USUniversity of Michigan–Ann Arbor · USWalter and Eliza Hall Institute of Medical Research · AU
Funding
Transcriptional and epigenetic heterogeneity of stem/progenitor cellsP01HL131477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Jason Daniel Buenrostro · 2017 to 2026
$24.6MFUNCTIONAL ISOLATION OF HUMAN HEMATOPOIETIC STEM CELLSR01DK050234 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 1995 to 2012
$3.7MBuilding the Hematopoietic Stem Cell NicheR01EB014703 · NIBIB · HARVARD UNIVERSITY · PI MOONEY, DAVID J, SCADDEN, DAVID T · 2011 to 2014
$3.1MThe mechanism of angiogenin-induced angiogenesisR01CA105241 · NCI · TUFTS MEDICAL CENTER · PI HU, GUO-FU · 2005 to 2015
$2.8MStem Cell Engagement of the NicheR01HL097794 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 2009 to 2012
$2.4MDeconvoluting the hematopoietic niche under stressR01DK107784 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KHARCHENKO, PETER V, SCADDEN, DAVID T · 2016 to 2019
$2.1MAngiogenin in ALS Pathobiology and TherapyR01NS065237 · NINDS · TUFTS MEDICAL CENTER · PI HU, GUO-FU · 2010 to 2014
$1.8MHarvard Stem Cell Institute Training Program for Pre- and Post-Doctoral FellowsT32HL087735 · NHLBI · HARVARD UNIVERSITY · PI SCADDEN, DAVID T · 2008 to 2012
$1.7MAge-associated chromatin changes in hematopoiesisK25AG037596 · NIA · HARVARD MEDICAL SCHOOL · PI KHARCHENKO, PETER V · 2010 to 2014
$749kMesenchyme Organizers of Organ Development, Maintenance and RepairR03HL096372 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 2009 to 2009
$44kRole of Angiogenin in Hematopoietic Stem Cell Quiescence and Self-renewalF31HL128127 · NHLBI · TUFTS UNIVERSITY BOSTON · PI GONCALVES, KEVIN A · 2015 to 2016
$43kCancer Research UK 11831NCI NIH HHS R01 CA105241NHLBI NIH HHS F31 HL128127NHLBI NIH HHS P01 HL131477NHLBI NIH HHS R01 HL097794NHLBI NIH HHS R03 HL096372NHLBI NIH HHS T32 HL087735NIA NIH HHS K25 AG037596NIBIB NIH HHS R01 EB014703NIDDK NIH HHS R01 DK050234NIDDK NIH HHS R01 DK107784NINDS NIH HHS R01 NS065237
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.
Indexed as
Stem Cell NicheAnimalsBone and BonesBone Marrow CellsCell LineageCell Self RenewalCell SeparationGene DeletionGene Expression ProfilingHematopoietic Stem CellsInterleukin-18Membrane GlycoproteinsRibonuclease, PancreaticSingle-Cell AnalysisTime FactorsTranscription, GeneticangiogeninInterleukin-18Membrane GlycoproteinsRibonuclease, PancreaticVascular Cell Adhesion Molecule-1
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