Differential transcriptional response profiles in human myeloid cell populations.
This study examines the transcriptional profiles of human adult brain-derived microglia in response to in vitro activating conditions previously used to polarize systemic myeloid cells into M1 and M2 phenotypes. A comparative study is done with monocyte-derived macrophages (MDMs), a myeloid cell type that also participates in disease relevant tissue injury and repair processes in the CNS. Current markers used to distinguish microglia and MDMs have been defined under homeostatic conditions. We observe that gene expression profiles of M1 microglia and MDMs overlap with an overrepresentation of immune-related pathways. M2 microglia and MDMs have distinct transcriptional signatures. Upregulated genes in M2 microglia favor neural-related pathways whereas upregulated genes in M2 MDMs are mostly involved in antigen presentation. Our microarray screen identifies candidate molecules that can potentially distinguish microglia and MDMs under all activation conditions. To be determined is how our observations made using conventional in vitro polarization translate into cellular responses to the complex combination of signals encountered in neurologic disease states.
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. Electronic address: luke.healy@mcgill.ca.
Luke M
LM
Healy
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Gabrielle
G
Perron
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
So-Yoon
SY
Won
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Vijayaraghava T S
VTS
Rao
Neuropathology, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Marie-Christine
MC
Guiot
Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada.
Craig
C
Moore
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Amit
A
Bar-Or
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Jack P
JP
Antel
D000328:Adult; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D016000:Cluster Analysis; D006801:Humans; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome
Microarray; Microglia; Monocyte-derived MDMs (MDMs); Multiple sclerosis (MS); Neuroinflammation