[en] Life-long brain function and mental health are critically determined by developmental processes occurring before birth. During mammalian pregnancy, maternal cells are transferred to the fetus. They are referred to as maternal microchimeric cells (MMc). Among other organs, MMc seed into the fetal brain, where their function is unknown. Here, we show that, in the offspring's developing brain in mice, MMc express a unique signature of sensome markers, control microglia homeostasis and prevent excessive presynaptic elimination. Further, MMc facilitate the oscillatory entrainment of developing prefrontal-hippocampal circuits and support the maturation of behavioral abilities. Our findings highlight that MMc are not a mere placental leak out, but rather a functional mechanism that shapes optimal conditions for healthy brain function later in life.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Schepanski, Steven ; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Chini, Mattia ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Sternemann, Veronika; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Urbschat, Christopher ; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Thiele, Kristin; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Sun, Ting; Institute of Medical Systems Biology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
Zhao, Yu ; Institute of Medical Systems Biology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Poburski, Mareike; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Woestemeier, Anna; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Thieme, Marie-Theres ; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Zazara, Dimitra E; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Alawi, Malik ; Bioinformatics Service Facility, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Fischer, Nicole; Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Heeren, Joerg ; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Vladimirov, Nikita ; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Woehler, Andrew ; Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany
Puelles, Victor G; III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Bonn, Stefan ; Institute of Medical Systems Biology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Gagliani, Nicola ; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Hanganu-Opatz, Ileana L; Institute of Developmental Neurophysiology, Center for Molecular Neurobiology Hamburg (ZMNH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany. hangop@zmnh.uni-hamburg.de
Arck, Petra C ; Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. p.arck@uke.de
We thank Agnes Wieczorek, Thomas Andreas, Annette Marquardt, Peggy Putthoff, Achim Dahlmann, Kristin Titze and Sandra Ehret for technical assistance. We thank Urte Matschl for support with Luminex measurements. The support from the staff members of the institutional core facilities (Microscopy Imaging Facility, FACS Sorting Core Unit, and Animal Housing Facility) and the NGS division of the Heinrich Pette Institute Hamburg (Dr. Daniela Indenbirken) is also appreciated. We thank Prof. Judith Eckert for support in yolk sac isolations. We thank Prof. Dr. Carlos A. Guzm\u00E1n for providing B6.129-Rag2tm1CgnIl2rgtm1Cgnmice, Dr. Jan-Eric Turner for providing Balb/c-Rag2\u2212/\u2212IL-2r\u03B3c\u2212/\u2212mice, and Dr. Nicola Wanner for providing C57BL/6-Gt(ROSA)26Sortm4(ACTB-tdTomato,-EGFP)Luo/J mice. This work was supported by German Research Foundation (HA 4466/10-1, HA4466/12-1, HA4466/20-1: 178316478\u00A0CRC 936 B5 to I.L.H.-O.; KFO296: AR232/25-2, FOR5068: AR232/29-1 to P.C.A.; CRC1192 to V.G.P.); the Federal Ministry of Education and Research (BMBF: eMed Consortia Fibromap to V.G.P); the European Research Council (ERC-2015-CoG 681577, MSCA-ITN-H2020-860563 to I.L.H.-O.); and State Research Funding, Authority for Science, Research and Equality, Hamburg, Germany (LFF-FV73 and LFF-FV76 to P.C.A. and\u00A0I.L.H.-O. respectively). S.S. received a fellowship from the Forschungsf\u00F6rderungsfond of the University Medical Center Hamburg-Eppendorf.We thank Agnes Wieczorek, Thomas Andreas, Annette Marquardt, Peggy Putthoff, Achim Dahlmann, Kristin Titze and Sandra Ehret for technical assistance. We thank Urte Matschl for support with Luminex measurements. The support from the staff members of the institutional core facilities (Microscopy Imaging Facility, FACS Sorting Core Unit, and Animal Housing Facility) and the NGS division of the Heinrich Pette Institute Hamburg (Dr. Daniela Indenbirken) is also appreciated. We thank Prof. Judith Eckert for support in yolk sac isolations. We thank Prof. Dr. Carlos A. Guzm\u00E1n for providing B6.129-Rag2Il2rg mice, Dr. Jan-Eric Turner for providing Balb/c-Rag2IL-2r\u03B3c mice, and Dr. Nicola Wanner for providing C57BL/6-Gt(ROSA)26Sor/J mice. This work was supported by German Research Foundation (HA 4466/10-1, HA4466/12-1, HA4466/20-1: 178316478 CRC 936 B5 to I.L.H.-O.; KFO296: AR232/25-2, FOR5068: AR232/29-1 to P.C.A.; CRC1192 to V.G.P.); the Federal Ministry of Education and Research (BMBF: eMed Consortia Fibromap to V.G.P); the European Research Council (ERC-2015-CoG 681577, MSCA-ITN-H2020-860563 to I.L.H.-O.); and State Research Funding, Authority for Science, Research and Equality, Hamburg, Germany (LFF-FV73 and LFF-FV76 to P.C.A. and I.L.H.-O. respectively). S.S. received a fellowship from the Forschungsf\u00F6rderungsfond of the University Medical Center Hamburg-Eppendorf. tm1Cgn tm1Cgn \u2212/\u2212 \u2212/\u2212 tm4(ACTB-tdTomato,-EGFP)Luo
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