The promise of stem cell research for neuropsychiatric disorders

被引:26
作者
Vaccarino, Flora M. [1 ,2 ]
Urban, Alexander Eckehart [3 ]
Stevens, Hanna E. [1 ]
Szekely, Anna [4 ]
Abyzov, Alexej [7 ]
Grigorenko, Elena L. [1 ,5 ,6 ]
Gerstein, Mark [7 ,8 ]
Weissman, Sherman [4 ]
机构
[1] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA
[3] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA
[4] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
[5] Yale Univ, Dept Psychol, New Haven, CT 06520 USA
[6] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA
[7] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
[8] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA
关键词
Developmental neurobiology; neural stem cells; induced pluripotent stem cells; neurons; next generation sequencing; copy number variation; COPY NUMBER VARIANTS; IN-VITRO; NEURAL DIFFERENTIATION; STRUCTURAL VARIATION; STROMAL CELLS; PLURIPOTENT; BRAIN; PROGENITORS; FIBROBLASTS; NEURONS;
D O I
10.1111/j.1469-7610.2010.02348.x
中图分类号
B844 [发展心理学(人类心理学)];
学科分类号
040202 ;
摘要
The study of the developing brain has begun to shed light on the underpinnings of both early and adult onset neuropsychiatric disorders. Neuroimaging of the human brain across developmental time points and the use of model animal systems have combined to reveal brain systems and gene products that may play a role in autism spectrum disorders, attention deficit hyperactivity disorder, obsessive compulsive disorder and many other neurodevelopmental conditions. However, precisely how genes may function in human brain development and how they interact with each other leading to psychiatric disorders is unknown. Because of an increasing understanding of neural stem cells and how the nervous system subsequently develops from these cells, we have now the ability to study disorders of the nervous system in a new way - by rewinding and reviewing the development of human neural cells. Induced pluripotent stem cells (iPSCs), developed from mature somatic cells, have allowed the development of specific cells in patients to be observed in real time. Moreover, they have allowed some neuronal-specific abnormalities to be corrected with pharmacological intervention in tissue culture. These exciting advances based on the use of iPSCs hold great promise for understanding, diagnosing and, possibly, treating psychiatric disorders. Specifically, examination of iPSCs from typically developing individuals will reveal how basic cellular processes and genetic differences contribute to individually unique nervous systems. Moreover, by comparing iPSCs from typically developing individuals and patients, differences at stem cell stages, through neural differentiation, and into the development of functional neurons may be identified that will reveal opportunities for intervention. The application of such techniques to early onset neuropsychiatric disorders is still on the horizon but has become a reality of current research efforts as a consequence of the revelations of many years of basic developmental neurobiological science.
引用
收藏
页码:504 / 516
页数:13
相关论文
共 68 条
  • [1] Alvarez-Buylla A, 2000, Prog Brain Res, V127, P1
  • [2] Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats
    Aubry, Laetitia
    Bugi, Aurore
    Lefort, Nathalie
    Rousseau, France
    Peschanski, Marc
    Perrier, Anselme L.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (43) : 16707 - 16712
  • [3] A bivalent chromatin structure marks key developmental genes in embryonic stem cells
    Bernstein, BE
    Mikkelsen, TS
    Xie, XH
    Kamal, M
    Huebert, DJ
    Cuff, J
    Fry, B
    Meissner, A
    Wernig, M
    Plath, K
    Jaenisch, R
    Wagschal, A
    Feil, R
    Schreiber, SL
    Lander, ES
    [J]. CELL, 2006, 125 (02) : 315 - 326
  • [4] Adult mice generated from induced pluripotent stem cells
    Boland, Michael J.
    Hazen, Jennifer L.
    Nazor, Kristopher L.
    Rodriguez, Alberto R.
    Gifford, Wesley
    Martin, Greg
    Kupriyanov, Sergey
    Baldwin, Kristin K.
    [J]. NATURE, 2009, 461 (7260) : 91 - U94
  • [5] Induced Pluripotent Stem Cells and Embryonic Stem Cells Are Distinguished by Gene Expression Signatures
    Chin, Mark H.
    Mason, Mike J.
    Xie, Wei
    Volinia, Stefano
    Singer, Mike
    Peterson, Cory
    Ambartsumyan, Gayane
    Aimiuwu, Otaren
    Richter, Laura
    Zhang, Jin
    Khvorostov, Ivan
    Ott, Vanessa
    Grunstein, Michael
    Lavon, Neta
    Benvenisty, Nissim
    Croce, Carlo M.
    Clark, Amander T.
    Baxter, Tim
    Pyle, April D.
    Teitell, Mike A.
    Pelegrini, Matteo
    Plath, Kathrin
    Lowry, William E.
    [J]. CELL STEM CELL, 2009, 5 (01) : 111 - 123
  • [6] Novel submicroscopic chromosomal abnormalities detected in autism spectrum disorder
    Christian, Susan L.
    Brune, Camille W.
    Sudi, Jyotsna
    Kumar, Ravinesh A.
    Liu, Shaung
    Karamohamed, Samer
    Badner, Judith A.
    Matsui, Seiichi
    Conroy, Jeffrey
    McQuaid, Devin
    Gergel, James
    Hatchwell, Eli
    Gilliam, T. Conrad
    Gershon, Elliot S.
    Nowak, Norma J.
    Dobyns, William B.
    Cook, Edwin H., Jr.
    [J]. BIOLOGICAL PSYCHIATRY, 2008, 63 (12) : 1111 - 1117
  • [7] Cohen M. A., 2007, CURR PROTOC CELL BIO
  • [8] Origins and functional impact of copy number variation in the human genome
    Conrad, Donald F.
    Pinto, Dalila
    Redon, Richard
    Feuk, Lars
    Gokcumen, Omer
    Zhang, Yujun
    Aerts, Jan
    Andrews, T. Daniel
    Barnes, Chris
    Campbell, Peter
    Fitzgerald, Tomas
    Hu, Min
    Ihm, Chun Hwa
    Kristiansson, Kati
    MacArthur, Daniel G.
    MacDonald, Jeffrey R.
    Onyiah, Ifejinelo
    Pang, Andy Wing Chun
    Robson, Sam
    Stirrups, Kathy
    Valsesia, Armand
    Walter, Klaudia
    Wei, John
    Tyler-Smith, Chris
    Carter, Nigel P.
    Lee, Charles
    Scherer, Stephen W.
    Hurles, Matthew E.
    [J]. NATURE, 2010, 464 (7289) : 704 - 712
  • [9] Adipose-Derived Mesenchymal Stem Cells Ameliorate Chronic Experimental Autoimmune Encephalomyelitis
    Constantin, Gabriela
    Marconi, Silvia
    Rossi, Barbara
    Angiari, Stefano
    Calderan, Laura
    Anghileri, Elena
    Gini, Beatrice
    Bach, Simone Dorothea
    Martinello, Marianna
    Bifari, Francesco
    Galie, Mirco
    Turano, Ermanna
    Budui, Simona
    Sbarbati, Andrea
    Krampera, Mauro
    Bonetti, Bruno
    [J]. STEM CELLS, 2009, 27 (10) : 2624 - 2635
  • [10] Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation
    Dezawa, M
    Kanno, H
    Hoshino, M
    Cho, H
    Matsumoto, N
    Itokazu, Y
    Tajima, N
    Yamada, H
    Sawada, H
    Ishikawa, H
    Mimura, T
    Kitada, M
    Suzuki, Y
    Ide, C
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (12) : 1701 - 1710