Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring

Michael J Nash; Evgenia Dobrinskikh; Taylor K Soderborg; Rachel C Janssen; Diana L Takahashi; Tyler A Dean; Oleg Varlamov; Jon D Hennebold; Maureen Gannon; Kjersti M Aagaard; Carrie E McCurdy; Paul Kievit; Bryan C Bergman; Kenneth L Jones; Eric M Pietras; Stephanie R Wesolowski; Jacob E Friedman

doi:10.1016/j.celrep.2023.112393

Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring

Cell Rep. 2023 Apr 25;42(4):112393. doi: 10.1016/j.celrep.2023.112393. Epub 2023 Apr 13.

Authors

Michael J Nash¹, Evgenia Dobrinskikh¹, Taylor K Soderborg¹, Rachel C Janssen², Diana L Takahashi³, Tyler A Dean³, Oleg Varlamov³, Jon D Hennebold⁴, Maureen Gannon⁵, Kjersti M Aagaard⁶, Carrie E McCurdy⁷, Paul Kievit³, Bryan C Bergman⁸, Kenneth L Jones⁹, Eric M Pietras⁸, Stephanie R Wesolowski¹, Jacob E Friedman¹⁰

Affiliations

¹ Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
² Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
³ Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
⁴ Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
⁵ Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37235, USA.
⁶ Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
⁷ Department of Human Physiology, University of Oregon, Eugene, OR 97403, USA.
⁸ Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁹ Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
¹⁰ Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: jed-friedman@ouhsc.edu.

Abstract

Maternal overnutrition increases inflammatory and metabolic disease risk in postnatal offspring. This constitutes a major public health concern due to increasing prevalence of these diseases, yet mechanisms remain unclear. Here, using nonhuman primate models, we show that maternal Western-style diet (mWSD) exposure is associated with persistent pro-inflammatory phenotypes at the transcriptional, metabolic, and functional levels in bone marrow-derived macrophages (BMDMs) from 3-year-old juvenile offspring and in hematopoietic stem and progenitor cells (HSPCs) from fetal and juvenile bone marrow and fetal liver. mWSD exposure is also associated with increased oleic acid in fetal and juvenile bone marrow and fetal liver. Assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling of HSPCs and BMDMs from mWSD-exposed juveniles supports a model in which HSPCs transmit pro-inflammatory memory to myeloid cells beginning in utero. These findings show that maternal diet alters long-term immune cell developmental programming in HSPCs with proposed consequences for chronic diseases featuring altered immune/inflammatory activation across the lifespan.

Keywords: CP: Immunology; DoHaD; Western-style diet; epigenetics; fatty acid; glycolysis; hematopoiesis; inflammation; macrophage; obesity.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Bone Marrow*
Diet, Western / adverse effects
Female
Hematopoietic Stem Cells*
Humans
Immunity, Innate
Primates

Abstract

Publication types

MeSH terms

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