Hofbauer cells and fetal brain microglia share transcriptional profiles and responses to maternal diet-induced obesity
Rebecca Batorsky,
Alexis M. Ceasrine,
Lydia L. Shook,
Sezen Kislal,
Evan A. Bordt,
Benjamin A. Devlin,
Roy H. Perlis,
Donna K. Slonim,
Staci D. Bilbo,
Andrea G. Edlow
Affiliations
Rebecca Batorsky
Data Intensive Studies Center, Tufts University, Medford, MA, USA
Alexis M. Ceasrine
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
Lydia L. Shook
Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, MA, USA
Sezen Kislal
Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, MA, USA
Evan A. Bordt
Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Benjamin A. Devlin
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA
Roy H. Perlis
Department of Psychiatry and Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Donna K. Slonim
Department of Computer Science, Tufts University, Medford, MA, USA
Staci D. Bilbo
Department of Psychology and Neuroscience, Duke University, Durham, NC, USA; Department of Neurobiology, Duke University, Durham, NC, USA; Lurie Center for Autism, Massachusetts General Hospital, Boston, MA, USA
Andrea G. Edlow
Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital Research Institute, Massachusetts General Hospital, Boston, MA, USA; Corresponding author
Summary: Maternal immune activation is associated with adverse offspring neurodevelopmental outcomes, many mediated by in utero microglial programming. As microglia remain inaccessible throughout development, identification of noninvasive biomarkers reflecting fetal brain microglial programming could permit screening and intervention. We used lineage tracing to demonstrate the shared ontogeny between fetal brain macrophages (microglia) and fetal placental macrophages (Hofbauer cells) in a mouse model of maternal diet-induced obesity, and single-cell RNA-seq to demonstrate shared transcriptional programs. Comparison with human datasets demonstrated conservation of placental resident macrophage signatures between mice and humans. Single-cell RNA-seq identified common alterations in fetal microglial and Hofbauer cell gene expression induced by maternal obesity, as well as sex differences in these alterations. We propose that Hofbauer cells, which are easily accessible at birth, provide insights into fetal brain microglial programs and may facilitate the early identification of offspring vulnerable to neurodevelopmental disorders.
