Human Glial Chimeric Mice to Define the Role of Glial Pathology in Human Disease
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Human Glial Chimeric Mice to Define the Role of Glial Pathology in Human Disease. / Mariani, John N; Zou, Lisa; Goldman, Steven A.
Oligodendrocytes. Vol. 1936 Springer, 2019. p. 311-331 (Methods in molecular biology (Clifton, N.J.)).Research output: Chapter in Book/Report/Conference proceeding › Book chapter › Research › peer-review
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TY - CHAP
T1 - Human Glial Chimeric Mice to Define the Role of Glial Pathology in Human Disease
AU - Mariani, John N
AU - Zou, Lisa
AU - Goldman, Steven A
PY - 2019
Y1 - 2019
N2 - Human glial progenitor cells (hGPCs) can engraft, expand, and differentiate into functional oligodendrocytes and astrocytes when transplanted neonatally into murine hosts, in which they outcompete the host glial pool to ultimately colonize and dominate the recipient brains. When congenitally hypomyelinated mutants are used as hosts, the donor hGPCs generate myelinogenic oligodendrocytes as well as astrocytes, so that the recipient mice develop a largely humanized white matter, with entirely human-derived myelin. In addition, by neonatally engrafting hGPCs derived from patient- and disease-specific pluripotent stem cells, glial chimeric mice may be produced in which large proportions of all macroglial cells are not only human but also patient and disease specific. Human glial chimeric mice thus provide intriguing preparations by which to investigate the species-specific contributions of human glia to both cognition and human-selective neurodegenerative and neuropsychiatric diseases, as well as the potential for therapeutic glial cell replacement in these disorders. This review presents an overview of the uses, characteristics, and limitations of the human glial chimeric brain model, while providing a step-by-step protocol for the establishment of these mice.
AB - Human glial progenitor cells (hGPCs) can engraft, expand, and differentiate into functional oligodendrocytes and astrocytes when transplanted neonatally into murine hosts, in which they outcompete the host glial pool to ultimately colonize and dominate the recipient brains. When congenitally hypomyelinated mutants are used as hosts, the donor hGPCs generate myelinogenic oligodendrocytes as well as astrocytes, so that the recipient mice develop a largely humanized white matter, with entirely human-derived myelin. In addition, by neonatally engrafting hGPCs derived from patient- and disease-specific pluripotent stem cells, glial chimeric mice may be produced in which large proportions of all macroglial cells are not only human but also patient and disease specific. Human glial chimeric mice thus provide intriguing preparations by which to investigate the species-specific contributions of human glia to both cognition and human-selective neurodegenerative and neuropsychiatric diseases, as well as the potential for therapeutic glial cell replacement in these disorders. This review presents an overview of the uses, characteristics, and limitations of the human glial chimeric brain model, while providing a step-by-step protocol for the establishment of these mice.
KW - Animals
KW - Astrocytes/cytology
KW - Chimera
KW - Disease Models, Animal
KW - Humans
KW - Mice
KW - Neurodegenerative Diseases/pathology
KW - Neuroglia/cytology
KW - Oligodendroglia/cytology
KW - Pluripotent Stem Cells/cytology
KW - White Matter/pathology
U2 - 10.1007/978-1-4939-9072-6_18
DO - 10.1007/978-1-4939-9072-6_18
M3 - Book chapter
C2 - 30820907
SN - 978-1-4939-9070-2
VL - 1936
T3 - Methods in molecular biology (Clifton, N.J.)
SP - 311
EP - 331
BT - Oligodendrocytes
PB - Springer
ER -
ID: 241830392