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other·preclinical research, biomedical research, immunology, endocrinology, nutrition·PMC10570400

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

Cell reports · 17 authors, 11 centres

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TL;DR

In a nonhuman primate model, maternal exposure to a Western-style diet was linked to persistent pro-inflammatory changes in fetal and juvenile hematopoietic and immune cells, even after offspring were weaned to a healthy diet. This suggests maternal nutrition can program long-term immune cell development.

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This preclinical study used a nonhuman primate model to investigate how maternal Western-style diet (mWSD) exposure during pregnancy and lactation affects offspring immune cell development. ATAC-seq data suggested that HSPCs transmit this pro-inflammatory memory to myeloid cells beginning *in utero*. Limitations include the indirect human relevance of the primate model and the need for further studies to confirm causal mechanisms.

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other

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preclinical research

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ORIGINAL PAPER

PMC10570400

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

Cell reports

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ABSTRACT

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.

CITATION EXPORT

Michael J. Nash, Evgenia Dobrinskikh, Taylor K. Soderborg et al.. Maternal diet alters long-term innate immune cell memory in fetal and juvenile hematopoietic stem and progenitor cells in nonhuman primate offspring. Cell reports. (2023). https://doi.org/10.1016/j.celrep.2023.112393

AUTHORS

17 · 11 CENTRES

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

1Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
3Division of Cardiometabolic Health, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
4Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA
5Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37235, USA
6Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX 77030, USA
7Department of Human Physiology, University of Oregon, Eugene, OR 97403, USA
8Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
9Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
10Senior author
11Lead contact