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Nature cell biology
01, 2020;22 (1): 38-48.

Combined single-cell and spatial transcriptomics reveal the molecular, cellular and spatial bone marrow niche organization.

Chiara Baccin, Jude Al-Sabah, Lars Velten, Patrick M Helbling, Florian Grünschläger, Pablo Hernández-Malmierca, César Nombela-Arrieta, Lars M Steinmetz, Andreas Trumpp, Simon Haas
Author Information
  1. Chiara Baccin: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. ORCID
  2. Jude Al-Sabah: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. ORCID
  3. Lars Velten: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. lars.velten@embl.de. ORCID
  4. Patrick M Helbling: Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland. ORCID
  5. Florian Grünschläger: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. ORCID
  6. Pablo Hernández-Malmierca: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. ORCID
  7. César Nombela-Arrieta: Department of Medical Oncology and Hematology, University Hospital and University of Zürich, Zürich, Switzerland. ORCID
  8. Lars M Steinmetz: Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany. larsms@embl.de. ORCID
  9. Andreas Trumpp: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. a.trumpp@dkfz-heidelberg.de. ORCID
  10. Simon Haas: Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany. s.haas@dkfz-heidelberg.de. ORCID
PMID: 31871321 DOI: 10.1038/s41556-019-0439-6

Abstract

The bone marrow constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular and spatial organization remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular, cellular and spatial composition of distinct bone marrow niches. This allowed us to transcriptionally profile all major bone-marrow-resident cell types, determine their localization and clarify sources of pro-haematopoietic factors. Our data demonstrate that Cxcl12-abundant-reticular (CAR) cell subsets (Adipo-CAR and Osteo-CAR) differentially localize to sinusoidal and arteriolar surfaces, act locally as 'professional cytokine-secreting cells' and thereby establish peri-vascular micro-niches. Importantly, the three-dimensional bone-marrow organization can be accurately inferred from single-cell transcriptome data using the RNA-Magnet algorithm described here. Together, our study reveals the cellular and spatial organization of bone marrow niches and offers a systematic approach to dissect the complex organization of whole organs.

References

  1. Nature. 2019 May;569(7755):222-228 [PMID: 30971824]
  2. Nat Commun. 2018 Jun 22;9(1):2449 [PMID: 29934585]
  3. Nature. 2013 Oct 31;502(7473):637-43 [PMID: 24107994]
  4. G3 (Bethesda). 2018 Jan 4;8(1):79-89 [PMID: 29118030]
  5. Trends Immunol. 2013 Dec;34(12):602-9 [PMID: 23631936]
  6. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  7. Methods Mol Biol. 2018;1711:243-259 [PMID: 29344893]
  8. Nature. 2012 Jan 25;481(7382):457-62 [PMID: 22281595]
  9. Blood. 2016 Aug 25;128(8):e20-31 [PMID: 27365425]
  10. Bioinformatics. 2015 Jan 15;31(2):166-9 [PMID: 25260700]
  11. Physiology (Bethesda). 2016 May;31(3):233-45 [PMID: 27053737]
  12. Nat Commun. 2016 Jul 08;7:12139 [PMID: 27387371]
  13. Nat Commun. 2015 Jul 22;6:7866 [PMID: 26198319]
  14. Cell. 2015 Jan 15;160(1-2):269-84 [PMID: 25594183]
  15. Science. 2016 Jul 1;353(6294):78-82 [PMID: 27365449]
  16. Nature. 2018 Aug;560(7719):494-498 [PMID: 30089906]
  17. Science. 2015 Apr 24;348(6233):aaa6090 [PMID: 25858977]
  18. PLoS One. 2011;6(11):e27156 [PMID: 22110609]
  19. Annu Rev Cell Dev Biol. 2016 Oct 6;32:649-675 [PMID: 27576121]
  20. Dev Cell. 2014 May 12;29(3):330-9 [PMID: 24823376]
  21. Nature. 2018 Nov;563(7731):347-353 [PMID: 30429548]
  22. Science. 2017 Dec 22;358(6370):1622-1626 [PMID: 29217582]
  23. Dev Cell. 2018 Mar 12;44(5):634-641.e4 [PMID: 29456137]
  24. Cell Stem Cell. 2014 Aug 7;15(2):154-68 [PMID: 24953181]
  25. Cell Syst. 2016 Oct 26;3(4):346-360.e4 [PMID: 27667365]
  26. Cell Stem Cell. 2016 Oct 6;19(4):530-543 [PMID: 27524439]
  27. Nat Commun. 2017 Dec 11;8(1):2032 [PMID: 29230012]
  28. Blood. 2016 Mar 31;127(13):1701-10 [PMID: 26796360]
  29. Nat Biotechnol. 2016 May;34(5):525-7 [PMID: 27043002]
  30. Nature. 2017 Jun 22;546(7659):533-538 [PMID: 28614297]
  31. Front Cell Neurosci. 2012 Jul 05;6:28 [PMID: 22783168]
  32. Nature. 2013 Mar 14;495(7440):231-5 [PMID: 23434755]
  33. Nature. 2010 Aug 12;466(7308):829-34 [PMID: 20703299]
  34. Nat Rev Mol Cell Biol. 2017 Aug;18(8):477-494 [PMID: 28537573]
  35. Nat Methods. 2015 May;12(5):453-7 [PMID: 25822800]
  36. Cell. 2018 Nov 1;175(4):1031-1044.e18 [PMID: 30318149]
  37. Nature. 2014 Jan 16;505(7483):327-34 [PMID: 24429631]
  38. Nat Cell Biol. 2017 Apr;19(4):271-281 [PMID: 28319093]
  39. Cell. 2018 Jul 26;174(3):716-729.e27 [PMID: 29961576]
  40. Immunity. 2018 Oct 16;49(4):627-639.e6 [PMID: 30314756]
  41. Nat Methods. 2018 May;15(5):359-362 [PMID: 29608555]
  42. Science. 2014 Mar 21;343(6177):1360-3 [PMID: 24578530]
  43. Nature. 2013 Mar 14;495(7440):227-30 [PMID: 23434756]
  44. Immunity. 2016 Dec 20;45(6):1219-1231 [PMID: 27913094]
  45. Methods Mol Biol. 2018;1649:95-110 [PMID: 29130192]
  46. Nature. 2018 Mar 1;555(7694):54-60 [PMID: 29466336]
  47. Cell. 1996 Feb 9;84(3):345-57 [PMID: 8608588]
  48. Nat Commun. 2018 Jun 28;9(1):2532 [PMID: 29955044]
  49. Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9): [PMID: 24003208]
  50. Nat Biotechnol. 2018 Jun;36(5):411-420 [PMID: 29608179]
  51. Cell. 2015 Dec 17;163(7):1663-77 [PMID: 26627738]
  52. Cell. 2015 Jan 15;160(1-2):285-98 [PMID: 25594184]
  53. Nat Cell Biol. 2017 Aug;19(8):891-903 [PMID: 28714970]
  54. Am J Nephrol. 2007;27(6):590-604 [PMID: 17823505]
  55. Cell. 2019 Jun 13;177(7):1915-1932.e16 [PMID: 31130381]
  56. Genome Biol. 2014 Feb 03;15(2):R29 [PMID: 24485249]
  57. Immunity. 2018 Apr 17;48(4):632-648 [PMID: 29669248]
  58. Nat Cell Biol. 2017 Mar;19(3):214-223 [PMID: 28218906]
  59. J Cell Sci. 2009 Jan 15;122(Pt 2):159-63 [PMID: 19118207]
  60. Cell. 2019 Jun 13;177(7):1888-1902.e21 [PMID: 31178118]
  61. Nat Methods. 2016 Jan;13(1):87-93 [PMID: 26524239]
  62. Nature. 2016 Apr 21;532(7599):323-8 [PMID: 27074509]
  63. Nat Biotechnol. 2017 Dec;35(12):1202-1210 [PMID: 29131149]
  64. Immunity. 2010 Sep 24;33(3):387-99 [PMID: 20850355]
  65. Exp Cell Res. 2004 Mar 10;294(1):244-53 [PMID: 14980518]
  66. Nat Immunol. 2018 Jan;19(1):85-97 [PMID: 29167569]
  67. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):466-471 [PMID: 30587579]
  68. Nat Commun. 2017 Jan 16;8:14049 [PMID: 28091601]
  69. Cancer Metastasis Rev. 2005 Sep;24(3):395-402 [PMID: 16258727]
  70. Immunity. 2006 Dec;25(6):977-88 [PMID: 17174120]

Grants

  1. 294542/European Research Council
  2. 742804/European Research Council
  3. P01 AG020752/NIA NIH HHS

MeSH Term

Animals
Bone Marrow
Bone Marrow Cells
Hematopoietic Stem Cells
Mesenchymal Stem Cells
Osteoblasts
Stem Cell Niche
Transcriptome
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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