Pre-pregnancy obesity is associated with an increased risk of infection and aberrant inflammatory responses in the offspring, but the underlying mechanisms remain largely unknown. In particular, very little is known about the effect of a Western-style diet on fetal hematopoiesis — the formation of blood cellular components, in animal models that resemble human development.
During late development, the fetal bone marrow becomes the major site where immune cells called macrophages and B-lymphocytes are produced via differentiation of hematopoietic stem and progenitor cells (HSPCs). In the new study, Varlamov and his collaborators analyzed the transcriptional landscape of fetal bone marrow HSPCs at single-cell resolution in fetal macaques exposed to a maternal high-fat, Western-style diet or a low-fat control diet.
The researcher were motivated to investigate how maternal obesity impacts the fetal immune system during pregnancy in nonhuman primates, representing the most relevant animal model for studying human development
The results demonstrated that a Western-style diet induced a hyperinflammatory response in HSPCs and fetal macrophages and suppressed the expression of B-cell development genes. Moreover, the unhealthy diet led to poor engraftment of fetal HSPCs in immunodeficient mice.
Maternal obesity greatly impacted the ability of fetal blood stem cells to produce B-lymphocytes, immune cells that make antibodies in response to infection, and made fetal blood stem cells more inflamed.
This study sets the stage for understanding the link between maternal obesity, prenatal nutrition, and diseases involving immune progeny of the HSPC compartment in children and highlights the need to better understand the susceptibility of the developing hematopoietic system to metabolic dysregulation over the lifetime
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, Benjamin J. Burwitz, Ilhem Messaoudi, Oleg Varlamov (November 3 , 2022). Maternal Western-style diet remodels the transcriptional landscape of fetal hematopoietic stem and progenitor cells in rhesus macaques. Stem Cell Reports. Retrieved from: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(22)00499-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671122004994%3Fshowall%3Dtrue