Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus

Juan M. Encinas; Tatyana V. Michurina; Natalia Peunova; June Hee Park; Julie Tordo; Daniel A. Peterson; Gord Fishell; Alex Koulakov; Grigori Enikolopov

doi:10.1016/j.stem.2011.03.010

Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus

Juan M. Encinas, Tatyana V. Michurina, Natalia Peunova, June Hee Park, Julie Tordo, Daniel A. Peterson, Gord Fishell, Alex Koulakov, Grigori Enikolopov

Center for Genomics and Systems Biology

Research output: Contribution to journal › Article › peer-review

Abstract

Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results indicate that adult hippocampal stem cells, upon exiting their quiescent state, rapidly undergo a series of asymmetric divisions to produce dividing progeny destined to become neurons and subsequently convert into mature astrocytes. Thus, the decrease in the number of neural stem cells is a division-coupled process and is directly related to their production of new neurons. We present a scheme of the neurogenesis cascade in the adult hippocampus that includes a proposed "disposable stem cell" model and accounts for the disappearance of hippocampal neural stem cells, the appearance of new astrocytes, and the age-related decline in the production of new neurons.

Original language	English (US)
Pages (from-to)	566-579
Number of pages	14
Journal	Cell Stem Cell
Volume	8
Issue number	5
DOIs	https://doi.org/10.1016/j.stem.2011.03.010
State	Published - May 6 2011

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

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10.1016/j.stem.2011.03.010

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title = "Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus",

abstract = "Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results indicate that adult hippocampal stem cells, upon exiting their quiescent state, rapidly undergo a series of asymmetric divisions to produce dividing progeny destined to become neurons and subsequently convert into mature astrocytes. Thus, the decrease in the number of neural stem cells is a division-coupled process and is directly related to their production of new neurons. We present a scheme of the neurogenesis cascade in the adult hippocampus that includes a proposed {"}disposable stem cell{"} model and accounts for the disappearance of hippocampal neural stem cells, the appearance of new astrocytes, and the age-related decline in the production of new neurons.",

author = "Encinas, {Juan M.} and Michurina, {Tatyana V.} and Natalia Peunova and Park, {June Hee} and Julie Tordo and Peterson, {Daniel A.} and Gord Fishell and Alex Koulakov and Grigori Enikolopov",

note = "Funding Information: We thank A. Krimmer for help with experiments, A. Joyner (MSKCC) for the Gli1-CreER line, J. Samanta (NYU) for the animals, Y. Lazebnik and B. Earnshaw for advice, and A. Sierra (BCM) and J. Banerji (MGH) for insightful discussions and comments. J.M.E. is a recipient of a Young Investigator Award from NARSAD. This work was supported by grants from the National Institutes of Health: from NIA to D.A.P., from NICHD to G.F., from NINDS and NIMH to G.E., and from NARSAD, NYSTEM, the Ira Hazan Fund, and The Ellison Medical Foundation to G.E. ",

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AU - Encinas, Juan M.

AU - Michurina, Tatyana V.

AU - Peunova, Natalia

AU - Park, June Hee

AU - Tordo, Julie

AU - Peterson, Daniel A.

AU - Fishell, Gord

AU - Koulakov, Alex

AU - Enikolopov, Grigori

N1 - Funding Information: We thank A. Krimmer for help with experiments, A. Joyner (MSKCC) for the Gli1-CreER line, J. Samanta (NYU) for the animals, Y. Lazebnik and B. Earnshaw for advice, and A. Sierra (BCM) and J. Banerji (MGH) for insightful discussions and comments. J.M.E. is a recipient of a Young Investigator Award from NARSAD. This work was supported by grants from the National Institutes of Health: from NIA to D.A.P., from NICHD to G.F., from NINDS and NIMH to G.E., and from NARSAD, NYSTEM, the Ira Hazan Fund, and The Ellison Medical Foundation to G.E.

PY - 2011/5/6

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N2 - Production of new neurons in the adult hippocampus decreases with age; this decline may underlie age-related cognitive impairment. Here we show that continuous depletion of the neural stem cell pool, as a consequence of their division, may contribute to the age-related decrease in hippocampal neurogenesis. Our results indicate that adult hippocampal stem cells, upon exiting their quiescent state, rapidly undergo a series of asymmetric divisions to produce dividing progeny destined to become neurons and subsequently convert into mature astrocytes. Thus, the decrease in the number of neural stem cells is a division-coupled process and is directly related to their production of new neurons. We present a scheme of the neurogenesis cascade in the adult hippocampus that includes a proposed "disposable stem cell" model and accounts for the disappearance of hippocampal neural stem cells, the appearance of new astrocytes, and the age-related decline in the production of new neurons.

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Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus

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