Specification of CNS macrophage subsets occurs postnatally in defined niches.

Masuda, Takahiro; Amann, Lukas; Monaco, Gianni; Sankowski, Roman; Staszewski, Ori; Krueger, Martin; Del Gaudio, Francesca; He, Liqun; Paterson, Neil; Nent, Elisa; Fernández-Klett, Francisco; Yamasaki, Ayato; Frosch, Maximilian; Fliegauf, Maximilian; Bosch, Lance Fredrick Pahutan; Ulupinar, Hatice; Hagemeyer, Nora; Schreiner, Dietmar; Dorrier, Cayce; Tsuda, Makoto; Grothe, Claudia; Joutel, Anne; Daneman, Richard; Betsholtz, Christer; Lendahl, Urban; Knobeloch, Klaus-Peter; Lämmermann, Tim; Priller, Josef; Kierdorf, Katrin; Prinz, Marco     «

Masuda, Takahiro; Amann, Lukas; Monaco, Gianni; Sankowski, Roman; Staszewski, Ori; Krueger, Martin; Del Gaudio, Francesca; He, Liqun; Paterson, Neil; Nent, Elisa; Fernández-Klett, Francisco; Yamasaki, Ayato; Frosch, Maximilian; Fliegauf, Maximilian; Bosch, Lance Fredrick Pahutan; Ulupinar, Hatice; Hagemeyer, Nora; Schreiner, Dietmar; Dorrier, Cayce; Tsuda, Makoto; Grothe, Claudia; Joutel, Anne; Daneman, Richard; Betsholtz, Christer; Lendahl, Urban; Knobeloch, Klaus-Peter; Lämmermann, Tim; Prille...     »

All tissue-resident macrophages of the central nervous system (CNS)-including parenchymal microglia, as well as CNS-associated macrophages (CAMs1) such as meningeal and perivascular macrophages2-7-are part of the CNS endogenous innate immune system that acts as the first line of defence during infections or trauma2,8-10. It has been suggested that microglia and all subsets of CAMs are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors11-15. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAM subsets in situ are poorly understood. Here we show, using fate-mapping systems, single-cell profiling and cell-specific mutants, that only meningeal macrophages and microglia share a common prenatal progenitor. By contrast, perivascular macrophages originate from perinatal meningeal macrophages only after birth in an integrin-dependent manner. The establishment of perivascular macrophages critically requires the presence of arterial vascular smooth muscle cells. Together, our data reveal a precisely timed process in distinct anatomical niches for the establishment of macrophage subsets in the CNS.      «

All tissue-resident macrophages of the central nervous system (CNS)-including parenchymal microglia, as well as CNS-associated macrophages (CAMs1) such as meningeal and perivascular macrophages2-7-are part of the CNS endogenous innate immune system that acts as the first line of defence during infections or trauma2,8-10. It has been suggested that microglia and all subsets of CAMs are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors11-1...     »