Identification of diverse astrocyte populations and their malignant analogs.
Astrocytes are the most abundant cell type in the brain, where they perform a wide array of functions, yet the nature of their cellular heterogeneity and how it oversees these diverse roles remains shrouded in mystery. Using an intersectional fluorescence-activated cell sorting-based strategy, we identified five distinct astrocyte subpopulations present across three brain regions that show extensive molecular diversity. Application of this molecular insight toward function revealed that these populations differentially support synaptogenesis between neurons. We identified correlative populations in mouse and human glioma and found that the emergence of specific subpopulations during tumor progression corresponded with the onset of seizures and tumor invasion. In sum, we have identified subpopulations of astrocytes in the adult brain and their correlates in glioma that are endowed with diverse cellular, molecular and functional properties. These populations selectively contribute to synaptogenesis and tumor pathophysiology, providing a blueprint for understanding diverse astrocyte contributions to neurological disease.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Chia-Ching
CC
John Lin
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Kwanha
K
Yu
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Asante
A
Hatcher
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Teng-Wei
TW
Huang
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.|Neurological Research Institute at Texas' Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Pediatrics, Division of Neurology, Texas Children's Hospital, Houston, Texas, USA.
Hyun Kyoung
HK
Lee
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.
Jeffrey
J
Carlson
Department of Neurological Sciences, University of Vermont, Vermont, Vermont, USA.
Matthew C
MC
Weston
Dan L. Duncan Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.
Fengju
F
Chen
Dan L. Duncan Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.
Yiqun
Y
Zhang
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Wenyi
W
Zhu
Department of Pathology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
Carrie A
CA
Mohila
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
Nabil
N
Ahmed
Neurological Research Institute at Texas' Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, USA.
Akash J
AJ
Patel
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.|Neurological Research Institute at Texas' Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Benjamin R
BR
Arenkiel
Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
Jeffrey L
JL
Noebels
Dan L. Duncan Cancer Center, Division of Biostatistics, Baylor College of Medicine, Houston, Texas, USA.|Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Chad J
CJ
Creighton
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.|Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.|Neurological Research Institute at Texas' Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.
Benjamin
B
Deneen
D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D005910:Glioma / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D000587:Oxidoreductases Acting on CH-NH Group Donors; D012640:Seizures / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*; D059467:Transcriptome; D000099295:Formyltetrahydrofolate Dehydrogenase
D000444:Aldehyde Dehydrogenase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000099295:Formyltetrahydrofolate Dehydrogenase