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 Jr; Benjamin J Burwitz; Ilhem Messaoudi; Oleg Varlamov

doi:10.1016/j.stemcr.2022.10.003

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

Stem Cell Reports. 2022 Dec 13;17(12):2595-2609. doi: 10.1016/j.stemcr.2022.10.003. Epub 2022 Nov 3.

Authors

Suhas Sureshchandra¹, Chi N Chan², Jacob J Robino³, Lindsay K Parmelee², Michael J Nash⁴, Stephanie R Wesolowski⁴, Eric M Pietras⁵, Jacob E Friedman⁶, Diana Takahashi², Weining Shen⁷, Xiwen Jiang⁷, Jon D Hennebold⁸, Devorah Goldman⁹, William Packwood¹⁰, Jonathan R Lindner¹¹, Charles T Roberts Jr¹², Benjamin J Burwitz¹³, Ilhem Messaoudi¹⁴, Oleg Varlamov¹⁵

Affiliations

¹ Department of Molecular Biology and Biochemistry, School of Biological Sciences, Institute for Immunology, Center for Virus Research, University of California-Irvine, Irvine, CA 92697, USA.
² Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, OR 97006.
³ Division of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR 97006.
⁴ Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁵ Department of Immunology and Microbiology, Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁶ Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
⁷ Department of Statistics, University of California-Irvine, Irvine, CA 92697, USA.
⁸ Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Beaverton, OR 97006; Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR 97239, USA.
⁹ Stem Cell Center, Oregon Health & Science University, Portland, OR 97239, USA.
¹⁰ Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR 97239, USA.
¹¹ Division of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR 97006; Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR 97239, USA.
¹² Division of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR 97006; Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
¹³ Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR 97006; Vaccine & Gene Therapy Institute, Beaverton, OR 97006, USA.
¹⁴ Department of Molecular Biology and Biochemistry, School of Biological Sciences, Institute for Immunology, Center for Virus Research, University of California-Irvine, Irvine, CA 92697, USA; Department of Immunology, Microbiology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40506, USA.
¹⁵ Division of Cardiometabolic Health, Oregon National Primate Research Center, Beaverton, OR 97006. Electronic address: varlamov@ohsu.edu.

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.

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

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Diet, Western* / adverse effects
Female
Humans
Macaca mulatta
Mice
Mice, Inbred NOD
Mice, SCID
Pregnancy
Stem Cells*

Abstract

Publication types

MeSH terms

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