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Human hematopoietic microenvironments

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  • Helene Bjoerg Kristensen, Syddansk Universitet
  • ,
  • Thomas Levin Andersen
  • Andrea Patriarca, Ospedale Maggiore
  • ,
  • Klaus Kallenbach, Sjællands Universitetshospital
  • ,
  • Birgit MacDonald, Syddansk Universitet
  • ,
  • Tanja Sikjaer
  • Charlotte Ejersted, Syddansk Universitet
  • ,
  • Jean Marie Delaisse, Syddansk Universitet

Dormancy of hematopoietic stem cells and formation of progenitors are directed by signals that come from the bone marrow microenvironment. Considerable knowledge has been gained on the murine hematopoietic stem cell microenvironment, while less so on the murine progenitor microenvironment and even less so on these microenvironments in humans. Characterization of these microenvironments is decisive for understanding hematopoiesis and finding new treatment modalities against bone marrow malignancies in the clinic. However, it is equally challenging, because hematopoietic stem cells are difficult to detect in the complex bone marrow landscape. In the present study we are characterizing the human hematopoietic stem cell and progenitor microenvironment. We obtained three adjacent bone marrow sections from ten healthy volunteers. One was used to identify a population of CD34+/CD38- “hematopoietic stem cells and multipotent progenitors” and a population of CD34+/CD38+ “progenitors” based on immunofluorescence pattern/intensity and cellular morphology. The other two were immunostained respectively for CD34/CD56 and for CD34/SMA. Using the combined information we performed a non-computer-assisted quantification of nine bone marrow components (adipocytes, megakaryocytes, bone surfaces, four different vessel types (arteries, capillaries, sinusoids and collecting sinuses), other “hematopoietic stem cells and multipotent progenitors” and other “progenitors”) within 30 μm of “hematopoietic stem cells and multipotent progenitors”, “progenitors”, and “random cell profiles”. We show that the microenvironment of the “hematopoietic stem cells and multipotent progenitors” is significantly enriched in sinusoids and megakaryocytes, while the microenvironment of the “progenitors” is significantly enriched in capillaries, other “progenitors”, bone surfaces and arteries.

TidsskriftPLOS ONE
Nummer4 April
StatusUdgivet - apr. 2021

Bibliografisk note

Funding Information:
Funding:HBKreceivedthefollowinggrants.The SouthernRegionresearchpost.doc.grant,no. 1362409;theZealandandSouthernRegion commonresearchgrant,no.14-001308;Overlaege JoergenWernerSchousoghustruElseMarie Schou, født Wonges, fond no. 85832. The funders didnotplayanyroleinthestudydesign,data collectionandanalysis,decisiontopublish,or preparationofthemanuscript.

Funding Information:
Funding: HBK received the following grants. The Southern Region research post.doc. grant, no. 1362409; the Zealand and Southern Region common research grant, no. 14-001308; Overlaege Joergen Werner Schous og hustru Else Marie Schou, f?dt Wonges, fond no. 85832. The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
Copyright: © 2021 Kristensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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