Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging

In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiesce...

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Published in:	Science (American Association for the Advancement of Science) Vol. 359; no. 6381; p. 1277
Main Authors:	Leeman, Dena S, Hebestreit, Katja, Ruetz, Tyson, Webb, Ashley E, McKay, Andrew, Pollina, Elizabeth A, Dulken, Ben W, Zhao, Xiaoai, Yeo, Robin W, Ho, Theodore T, Mahmoudi, Salah, Devarajan, Keerthana, Passegué, Emmanuelle, Rando, Thomas A, Frydman, Judith, Brunet, Anne
Format:	Journal Article
Language:	English
Published:	United States 16.03.2018
Subjects:	Aging - physiology Animals Cell Division Cellular Senescence Lysosomes - physiology Mice Mice, Inbred C57BL Neural Stem Cells - physiology
ISSN:	1095-9203, 1095-9203
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Abstract	In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.
AbstractList	In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state. In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.
Author	Zhao, Xiaoai McKay, Andrew Devarajan, Keerthana Frydman, Judith Leeman, Dena S Ruetz, Tyson Brunet, Anne Mahmoudi, Salah Webb, Ashley E Pollina, Elizabeth A Passegué, Emmanuelle Hebestreit, Katja Yeo, Robin W Ho, Theodore T Dulken, Ben W Rando, Thomas A
Author_xml	– sequence: 1 givenname: Dena S orcidid: 0000-0003-4338-5433 surname: Leeman fullname: Leeman, Dena S organization: Cancer Biology Program, Stanford University, Stanford, CA 94305, USA – sequence: 2 givenname: Katja orcidid: 0000-0002-6404-9917 surname: Hebestreit fullname: Hebestreit, Katja organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 3 givenname: Tyson orcidid: 0000-0001-5526-1978 surname: Ruetz fullname: Ruetz, Tyson organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 4 givenname: Ashley E orcidid: 0000-0002-0441-2307 surname: Webb fullname: Webb, Ashley E organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 5 givenname: Andrew surname: McKay fullname: McKay, Andrew organization: Biology Graduate Program, Stanford University, Stanford, CA 94305, USA – sequence: 6 givenname: Elizabeth A orcidid: 0000-0003-3102-3160 surname: Pollina fullname: Pollina, Elizabeth A organization: Cancer Biology Program, Stanford University, Stanford, CA 94305, USA – sequence: 7 givenname: Ben W orcidid: 0000-0001-5042-3712 surname: Dulken fullname: Dulken, Ben W organization: Stanford Medical Scientist Training Program, Stanford University, Stanford, CA 94305, USA – sequence: 8 givenname: Xiaoai orcidid: 0000-0001-6602-0838 surname: Zhao fullname: Zhao, Xiaoai organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 9 givenname: Robin W surname: Yeo fullname: Yeo, Robin W organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 10 givenname: Theodore T orcidid: 0000-0001-8395-5547 surname: Ho fullname: Ho, Theodore T organization: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA – sequence: 11 givenname: Salah orcidid: 0000-0002-8468-6155 surname: Mahmoudi fullname: Mahmoudi, Salah organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 12 givenname: Keerthana orcidid: 0000-0003-4435-1905 surname: Devarajan fullname: Devarajan, Keerthana organization: Department of Genetics, Stanford University, Stanford, CA 94305, USA – sequence: 13 givenname: Emmanuelle surname: Passegué fullname: Passegué, Emmanuelle organization: The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA – sequence: 14 givenname: Thomas A orcidid: 0000-0001-5843-8564 surname: Rando fullname: Rando, Thomas A organization: Glenn Center for the Biology of Aging at Stanford University, Stanford, CA 94305, USA – sequence: 15 givenname: Judith surname: Frydman fullname: Frydman, Judith organization: Department of Biology, Stanford University, Stanford, CA 94305, USA – sequence: 16 givenname: Anne orcidid: 0000-0002-4608-6845 surname: Brunet fullname: Brunet, Anne email: anne.brunet@stanford.edu organization: Glenn Center for the Biology of Aging at Stanford University, Stanford, CA 94305, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/29590078$$D View this record in MEDLINE/PubMed
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References	29727677 - Cell Stem Cell. 2018 May 3;22(5):619-620. doi: 10.1016/j.stem.2018.04.017 29643417 - Nat Rev Mol Cell Biol. 2018 Jun;19(6):346-347. doi: 10.1038/s41580-018-0012-3
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Snippet	In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that...
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SubjectTerms	Aging - physiology Animals Cell Division Cellular Senescence Lysosomes - physiology Mice Mice, Inbred C57BL Neural Stem Cells - physiology
Title	Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging
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