Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques

Suhas Sureshchandra, Chi N. Chan, Jacob J. Robino, Lindsay K. Parmelee, Michael J. Nash, Stephanie R. Wesolowski, Eric M. Pietras, Jacob E. Friedman, Diana Takahashi, Weining Shen, Xiwen Jiang, Jon D. Hennebold, Devorah Goldman, William Packwood, Jonathan R. Lindner, Charles T. Roberts, Benjamin J. Burwitz, Ilhem Messaoudi, Oleg Varlamov

Research output: Contribution to journalArticlepeer-review

Abstract

Maternal obesity adversely impacts the in utero metabolic environment, but its effect on fetal hematopoiesis remains incompletely understood. During late development, the fetal bone marrow (FBM) becomes the major site where macrophages and B lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we analyzed the transcriptional landscape of FBM HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat Western-style diet (WSD) or a low-fat control diet. We demonstrate that maternal WSD induces a proinflammatory response in FBM HSPCs and fetal macrophages. In addition, maternal WSD consumption suppresses the expression of B cell development genes and decreases the frequency of FBM B cells. Finally, maternal WSD leads to poor engraftment of fetal HSPCs in nonlethally irradiated immunodeficient NOD/SCID/IL2rγ−/− mice. Collectively, these data demonstrate for the first time that maternal WSD impairs fetal HSPC differentiation and function in a translationally relevant nonhuman primate model.

Original languageEnglish (US)
Pages (from-to)2595-2609
Number of pages15
JournalStem Cell Reports
Volume17
Issue number12
DOIs
StatePublished - Dec 13 2022

Keywords

  • B lymphocytes
  • bone marrow
  • fetal development
  • hematopoietic stem and progenitor cells
  • high-fat diet
  • macrophages
  • maternal programming
  • monocytes
  • nonhuman primates
  • obesity

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques'. Together they form a unique fingerprint.

Cite this