Induced pluripotent stem (iPS) cells as in vitro models of human neurogenetic disorders.
The recent discovery of genomic reprogramming of human somatic cells into induced pluripotent stem cells offers an innovative and relevant approach to the study of human genetic and neurogenetic diseases. By reprogramming somatic cells from patient samples, cell lines can be isolated that self-renew indefinitely and have the potential to develop into multiple different tissue lineages. Additionally, the rapid progress of research on human embryonic stem cells has led to the development of sophisticated in vitro differentiation protocols that closely mimic mammalian development. In particular, there have been significant advances in differentiating human pluripotent stem cells into defined neuronal types. Here, we summarize the experimental approaches employed in the rapidly evolving area of somatic cell reprogramming and the methodologies for differentiating human pluripotent cells into neurons. We also discuss how the availability of patient-specific fibroblasts offers a unique opportunity for studying and modeling the effects of specific gene defects on human neuronal development in vitro and for testing small molecules or other potential therapies for the relevant neurogenetic disorders.
Chamberlain
Stormy J
SJ
Department of Genetics and Developmental Biology, Stem Cell Institute, University of Connecticut Health Center, Farmington, CT, USA.
Li
Xue-Jun
XJ
Lalande
Marc
M
D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D008957:Models, Genetic; D008959:Models, Neurological; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology*
Cell. 2002 Aug 9;110(3):385-97
12176325
Stem Cells. 2005 Jun-Jul;23(6):781-90
15917474
EMBO J. 1997 Nov 3;16(21):6510-20
9351832
Hum Mol Genet. 1999 Jul;8(7):1177-83
10369862
J Embryol Exp Morphol. 1962 Dec;10:622-40
13951335
Nat Biotechnol. 2001 Dec;19(12):1129-33
11731781
Nature. 2008 Jul 31;454(7204):646-50
18594515
Stem Cells. 2008 Aug;26(8):1998-2005
18511599
Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1580-5
11818560
Nat Biotechnol. 2008 Feb;26(2):215-24
18246062
Neuron. 2000 Oct;28(1):69-80
11086984
Curr Opin Neurobiol. 2001 Feb;11(1):43-9
11179871
Dev Biol. 1962 Apr;4:256-73
13903027
J Neurosci. 2007 Mar 21;27(12):3069-77
17376968
Nature. 2007 Jul 19;448(7151):313-7
17554338
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13821-6
17693548
Science. 2005 Aug 26;309(5739):1369-73
16123299
Nature. 2008 Jan 10;451(7175):141-6
18157115
Cell. 2006 Aug 25;126(4):663-76
16904174
Neuron. 1998 Oct;21(4):799-811
9808466
Neurobiol Dis. 2002 Mar;9(2):149-59
11895368
Stem Cells. 2008 Apr;26(4):886-93
18238853
Glia. 2005 Feb;49(3):385-96
15538751
Science. 2008 Aug 29;321(5893):1218-21
18669821
Nat Biotechnol. 2008 Jan;26(1):101-6
18059259
Nature. 2007 Jul 19;448(7151):318-24
17554336
Dev Biol. 2006 Feb 15;290(2):287-96
16406324
Cell. 1998 May 29;93(5):755-66
9630220
Stem Cells. 2004;22(5):669-74
15342931
Nat Biotechnol. 2005 Feb;23(2):215-21
15685164
Cell. 1995 Jan 13;80(1):155-65
7813012
Science. 2005 Jun 17;308(5729):1747-8
15905363
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):2883-8
18287077
Stem Cells. 2006 Jan;24(1):168-76
16210403
DNA Repair (Amst). 2008 Jul 1;7(7):1110-20
18463003
Nature. 1997 Feb 27;385(6619):810-3
9039911
Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12543-8
15310843
Stem Cells Dev. 2004 Aug;13(4):372-81
15345131
Nat Rev Neurosci. 2001 Feb;2(2):92-8
11252999
Methods. 2008 Jun;45(2):142-58
18593611
Stem Cells. 2007 Feb;25(2):419-24
17053214
Cell Stem Cell. 2008 Jun 5;2(6):525-8
18522845
Nat Biotechnol. 2008 Jul;26(7):795-7
18568017
BMC Neurosci. 2003 Oct 22;4:27
14572319
Stem Cells. 2007 Jun;25(6):1511-20
17332508
Cell. 2007 Nov 30;131(5):861-72
18035408
Nat Rev Genet. 2000 Oct;1(1):20-9
11262869
Hum Mol Genet. 2003 Apr 15;12(8):837-47
12668607
N Engl J Med. 2007 Mar 29;356(13):1289-91
17392298
Acta Neuropathol. 2008 Sep;116(3):223-34
18629520
Cell Res. 2008 May;18(5):600-3
18414447
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6307-11
10339583
Cell. 2008 Sep 5;134(5):877-86
18691744
Cell Mol Life Sci. 2007 Apr;64(7-8):947-60
17347796
Nature. 2008 Jul 3;454(7200):49-55
18509334
Mol Cell Neurosci. 2007 Mar;34(3):310-23
17196394
Science. 2007 Dec 21;318(5858):1917-20
18029452
Methods Mol Biol. 2006;331:169-77
16881517