Human fetal microglia acquire homeostatic immune-sensing properties early in development

被引:134
作者
Kracht, L. [1 ]
Borggrewe, M. [1 ]
Eskandar, S. [1 ,2 ]
Brouwer, N. [1 ]
Lopes, S. M. Chuva de Sousa [3 ,4 ]
Laman, J. D. [1 ]
Scherjon, S. A. [2 ]
Prins, J. R. [2 ]
Kooistra, S. M. [1 ]
Eggen, B. J. L. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Sect Mol Neurobiol, Dept Biomed Sci Cells & Syst, Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands
[3] Leiden Univ, Med Ctr, Dept Anat & Embryol, Leiden, Netherlands
[4] Ghent Univ Hosp, Dept Reprod Med, Ghent, Belgium
关键词
READ ALIGNMENT; RNA-SEQ; DIFFERENTIATION; MYELINOGENESIS; TURNOVER; BINDING; CELLS; PU.1; AGE;
D O I
10.1126/science.aba5906
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Microglia, immune cells of the central nervous system (CNS), are important for tissue development and maintenance and are implicated in CNS disease, but we lack understanding of human fetal microglia development. Single-cell gene expression and bulk chromatin profiles of microglia at 9 to 18 gestational weeks (GWs) of human fetal development were generated. Microglia were heterogeneous at all studied GWs. Microglia start to mature during this developmental period and increasingly resemble adult microglia with CNS-surveilling properties. Chromatin accessibility increases during development with associated transcriptional networks reflective of adult microglia. Thus, during early fetal development, microglia progress toward a more mature, immune-sensing competent phenotype, and this might render the developing human CNS vulnerable to environmental perturbations during early pregnancy.
引用
收藏
页码:530 / +
页数:25
相关论文
共 57 条
[1]  
Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/NMETH.4463, 10.1038/nmeth.4463]
[2]   Epigenetic regulation of brain region-specific microglia clearance activity [J].
Ayata, Pinar ;
Badimon, Ana ;
Strasburger, Hayley J. ;
Duff, Mary Kaye ;
Montgomery, Sarah E. ;
Loh, Yong-Hwee E. ;
Ebert, Anja ;
Pimenova, Anna A. ;
Ramirez, Brianna R. ;
Chan, Andrew T. ;
Sullivan, Josefa M. ;
Purushothaman, Immanuel ;
Scarpa, Joseph R. ;
Goate, Alison M. ;
Busslinger, Meinrad ;
Shen, Li ;
Losic, Bojan ;
Schaefer, Anne .
NATURE NEUROSCIENCE, 2018, 21 (08) :1049-+
[3]   VISTA expression by microglia decreases during inflammation and is differentially regulated in CNS diseases [J].
Borggrewe, Malte ;
Grit, Corien ;
Den Dunnen, Wilfred F. A. ;
Burm, Saskia M. ;
Bajramovic, Jeffrey J. ;
Noelle, Randolph J. ;
Eggen, Bart J. L. ;
Laman, Jon D. .
GLIA, 2018, 66 (12) :2645-2658
[4]  
Buenrostro Jason D, 2015, Curr Protoc Mol Biol, V109, DOI 10.1002/0471142727.mb2129s109
[5]  
Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/NMETH.2688, 10.1038/nmeth.2688]
[6]   Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development [J].
Croen, Lisa A. ;
Qian, Yinge ;
Ashwood, Paul ;
Zerbo, Ousseny ;
Schendel, Diana ;
Pinto-Martin, Jennifer ;
Fallin, M. Daniele ;
Levy, Susan ;
Schieve, Laura A. ;
Yeargin-Allsopp, Marshalyn ;
Sabourin, Katherine R. ;
Ames, Jennifer L. .
AUTISM RESEARCH, 2019, 12 (10) :1551-1561
[7]   MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data [J].
Finak, Greg ;
McDavid, Andrew ;
Yajima, Masanao ;
Deng, Jingyuan ;
Gersuk, Vivian ;
Shalek, Alex K. ;
Slichter, Chloe K. ;
Miller, Hannah W. ;
McElrath, M. Juliana ;
Prlic, Martin ;
Linsley, Peter S. ;
Gottardo, Raphael .
GENOME BIOLOGY, 2015, 16
[8]   Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging [J].
Fueger, Petra ;
Hefendehl, Jasmin K. ;
Veeraraghavalu, Karthik ;
Wendeln, Ann-Christin ;
Schlosser, Christine ;
Obermueller, Ulrike ;
Wegenast-Braun, Bettina M. ;
Neher, Jonas J. ;
Martus, Peter ;
Kohsaka, Shinichi ;
Thunemann, Martin ;
Feil, Robert ;
Sisodia, Sangram S. ;
Skodras, Angelos ;
Jucker, Mathias .
NATURE NEUROSCIENCE, 2017, 20 (10) :1371-+
[9]   Transcriptomic analysis of purified human cortical microglia reveals age-associated changes [J].
Galatro, Thais F. ;
Holtman, Inge R. ;
Lerario, Antonio M. ;
Vainchtein, Ilia D. ;
Brouwer, Nieske ;
Sola, Paula R. ;
Veras, Mariana M. ;
Pereira, Tulio F. ;
Leite, Renata E. P. ;
Moller, Thomas ;
Wes, Paul D. ;
Sogayar, Mari C. ;
Laman, Jon D. ;
den Dunnen, Wilfred ;
Pasqualucci, Carlos A. ;
Oba-Shinjo, Sueli M. ;
Boddeke, Erik W. G. M. ;
Marie, Suely K. N. ;
Eggen, Bart J. L. .
NATURE NEUROSCIENCE, 2017, 20 (08) :1162-+
[10]  
Galatro TF, 2017, METHODS MOL BIOL, V1559, P333, DOI 10.1007/978-1-4939-6786-5_23