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Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue

Authors
  • Gavin, Kathleen M.1, 2
  • Sullivan, Timothy M.1, 2
  • Maltzahn, Joanne K.1, 2
  • Rahkola, Jeremy T.3
  • Acosta, Alistair S.4
  • Kohrt, Wendy M.1, 2
  • Majka, Susan M.5, 2, 2
  • Klemm, Dwight J.1, 2, 2
  • 1 Education and Clinical Center (GRECC), Rocky Mountain Regional VA Medical Center, USA
  • 2 University of Colorado Anschutz Medical Campus, USA
  • 3 University of Colorado Anschutz Medical Campus, Rocky Mountain Regional VA Medical Center, USA
  • 4 University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, USA
  • 5 National Jewish Health, USA
Type
Published Article
Journal
Adipocyte
Publisher
Landes Bioscience
Publication Date
Aug 18, 2021
Volume
10
Issue
1
Pages
394–407
Identifiers
DOI: 10.1080/21623945.2021.1957290
PMID: 34404315
PMCID: PMC8381847
Source
PubMed Central
Keywords
Disciplines
  • Research Paper
License
Unknown

Abstract

Some adipocytes are produced from bone marrow hematopoietic stem cells. In vitro studies previously indicated that these bone marrow-derived adipocytes (BMDAs) were generated from adipose tissue macrophage (ATM) that lose their hematopoietic markers and acquire mesenchymal markers prior to terminal adipogenic differentiation. Here we interrogated whether this hematopoietic-to-mesenchymal transition drives BMDA production In vitro . We generated transgenic mice in which the lysozyme gene promoter (LysM) indelibly labeled ATM with green fluorescent protein (GFP). We discovered that adipose stroma contained a population of LysM-positive myeloid cells that simultaneously expressed hematopoietic/myeloid markers (CD45 and CD11b), and mesenchymal markers (CD29, PDGFRa and Sca-1) typically found on conventional adipocyte progenitors. These cells were capable of adipogenic differentiation In vitro and In vitro , while other stromal populations deficient in PDGFRa and Sca-1 were non-adipogenic. BMDAs and conventional adipocytes expressed common fat cell markers but exhibited little or no expression of hematopoietic and mesenchymal progenitor cell markers. The data indicate that BMDAs are produced from ATM simultaneously expressing hematopoietic and mesenchymal markers rather than via a stepwise hematopoietic-to-mesenchymal transition. Because BMDA production is stimulated by high fat feeding, their production from hematopoietic progenitors may maintain adipocyte production when conventional adipocyte precursors are diminished.

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