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
Affiliations
Michael J. Nash
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Evgenia Dobrinskikh
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Taylor K. Soderborg
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Rachel C. Janssen
Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Diana L. Takahashi
Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
Tyler A. Dean
Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
Oleg Varlamov
Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
Jon D. Hennebold
Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
Maureen Gannon
Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37235, USA
Kjersti M. Aagaard
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Carrie E. McCurdy
Department of Human Physiology, University of Oregon, Eugene, OR 97403, USA
Paul Kievit
Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
Bryan C. Bergman
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Kenneth L. Jones
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Eric M. Pietras
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Stephanie R. Wesolowski
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Jacob E. Friedman
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; Corresponding author
Summary: 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.
