Bone marrow adipocytes support hematopoietic stem cell survival

Domenico Mattiucci, Giulia Maurizi, Valerio Izzi, Lorenzo Cenci, Marco Ciarlantini, Stefania Mancini, Emanuela Mensà, Raffaele Pascarella, Marco Vivarelli, Attilio Olivieri, Pietro Leoni, Antonella Poloni

Research output: Contribution to journalArticle

Abstract

In bone marrow (BM), hematopoietic elements are mingled with adipocytes (BM-A), which are the most abundant stromal component in the niche. BM-A progressively increase with aging, eventually occupying up to 50% of BM cavities. In this work, the role played by BM-A was explored by studying primary human BM-A isolated from hip surgery patients at the molecular level, through microarray analysis, and at the functional level, by assessing their relationship with primary human hematopoietic stem cells (HSC) by the long-term culture initiating cell (LTC-IC) assay. Findings demonstrated that BM-A are capable of supporting HSC survival in the LTC-IC assay, since after 5 weeks of co-culture, HSC were still able to proliferate and differentiate. Furthermore, critical molecules such as C-X-C motif chemokine 12 (CXCL12), interleukin (IL)-8, colony-stimulating factor 3 (CSF3), and leukaemia inhibitory factor (LIF), were expressed at similar levels in BM-A and in primary human BM mesenchymal stromal cells (BM-MSC), whereas IL-3 was higher in BM-A. Interestingly, BM-A displayed a different gene expression profile compared with subcutaneous adipose tissue adipocytes (AT-A) collected from abdominal surgery patients, especially in terms of regulation of lipid metabolism, stemness genes, and white-to-brown differentiation pathways. Accordingly, analysis of the gene pathways involved in hematopoiesis regulation showed that BM-A are more closely related to BM-MSC than to AT-A. The present data suggest that BM-A play a supporting role in the hematopoietic niche and directly sustain HSC survival.

Original languageEnglish
Pages (from-to)1500-1511
Number of pages12
JournalJournal of Cellular Physiology
Volume233
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Keywords

  • adipose tissue
  • bone marrow adipocytes
  • bone marrow fat
  • hematopoiesis
  • hematopoietic stem cell

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Mattiucci, D., Maurizi, G., Izzi, V., Cenci, L., Ciarlantini, M., Mancini, S., Mensà, E., Pascarella, R., Vivarelli, M., Olivieri, A., Leoni, P., & Poloni, A. (2018). Bone marrow adipocytes support hematopoietic stem cell survival. Journal of Cellular Physiology, 233(2), 1500-1511. https://doi.org/10.1002/jcp.26037