Ascl1 lineage cells contribute to ischemia-induced neurogenesis and oligodendrogenesis.
Neural and oligodendrocyte progenitor cells in the adult brain express Ascl1 (also known as Mash1), a basic helix-loop-helix transcription factor. We examined the progeny and fate of this progenitor population in adult male Ascl1-CreER(TM);R26R-stop-yellow fluorescent protein mice subjected to right middle cerebral occlusion over 60 days after stroke using inducible Cre recombination to label Ascl1-expressing cells at poststroke days 2 to 6 in vivo. Seven days after stroke, a substantial increase in Ascl1 lineage cells was detected in the ipsilateral subventricular zone (SVZ), striatum, and corpus callosum. These cells exhibited proliferating progenitor cell phenotypes (Sox2(+), BrdU(+), and Ki67(+)). Although Ascl1 lineage cells in the ipsilateral SVZ gradually decreased during 14 to 60 days after stroke, Ascl1 lineage cells in the ischemic striatum revealed a remarkable increase during this period. Thirty and sixty days after stroke, Ascl1 lineage cells in the ischemic striatum gave rise to GABAergic neurons and mature oligodendrocytes. In contrast, none of the Ascl1 lineage cells in the contralateral striatum exhibited neuronal and oligodendrocyte phenotypes. Moreover, Ascl1 lineage cells in the corpus callosum were only fated to become mature oligodendrocytes. Our data suggest that Ascl1 lineage cells contribute to stroke-induced neurogenesis and oligodendrogenesis in the adult ischemic brain.
Zhang
Rui Lan
RL
Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Chopp
Michael
M
Roberts
Cindi
C
Jia
Longfei
L
Wei
Min
M
Lu
Mei
M
Wang
Xinli
X
Pourabdollah
Siamak
S
Zhang
Zheng Gang
ZG
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine; D019070:Cell Lineage; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000473:pathology; D003337:Corpus Callosum / Q000473:pathology; D004965:Estrogen Antagonists / Q000627:therapeutic use; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000473:pathology; D013629:Tamoxifen / Q000627:therapeutic use
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004965:Estrogen Antagonists; D008164:Luminescent Proteins; D013629:Tamoxifen; C499317:Ascl1 protein, mouse