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

• DOI: 10.1016/j.stemcr.2022.10.003
• Publication Date: 2022-11-03T14:43:52Z
• Authors: Suhas Sureshchandra; Chi N. Chan; Jacob J. Robino; Lindsay K. Parmelee; Michael J. Nash; Stephanie R. Weso...; 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
• Keywords: 0301 basic medicine; obesity; bone marrow; nonhuman primates; fetal development; hematopoietic stem and progenitor cells; Clinical Sciences; Reproductive health and childbirth; Mice, SCID; Regenerative Medicine; SCID; Article; Mice; 03 medical and health sciences; Stem Cell Research - Nonembryonic - Human; Pregnancy; Mice, Inbred NOD; maternal programming; Humans; Animals; Obesity; Nutrition; Pediatric; 2. Zero hunger; Stem Cells; Biological Sciences; Stem Cell Research; Macaca mulatta; Diet; macrophages; high-fat diet; Diet, Western; Biochemistry and cell biology; Inbred NOD; Stem Cell Research - Nonembryonic - Non-Human; Female; Biochemistry and Cell Biology; monocytes; Western; B lymphocytes

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.