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Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

Front Biol    2013, Vol. 8 Issue (1) : 50-59    https://doi.org/10.1007/s11515-012-1198-y
REVIEW
Alternative splicing switching in stem cell lineages
Iouri CHEPELEV1, Xin CHEN2()
1. Systems Biology Center, National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA; 2. Department of Biology, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA
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Abstract

The application of stem cells to regenerative medicine depends on a thorough understanding of the molecular mechanisms underlying their pluripotency. Many studies have identified key transcription factor-regulated transcriptional networks and chromatin landscapes of embryonic and a number of adult stem cells. In addition, recent publications have revealed another interesting molecular feature of stem cells— a distinct alternative splicing pattern. Thus, it is possible that both the identity and activity of stem cells are maintained by stem cell-specific mRNA isoforms, while switching to different isoforms ensures proper differentiation. In this review, we will discuss the generality of mRNA isoform switching and its interaction with other molecular mechanisms to regulate stem cell pluripotency, as well as the reprogramming process in which differentiated cells are induced to become pluripotent stem cell-like cells (iPSCs).

Keywords alternative splicing      embryonic stem cells      adult stem cells      stem cell maintenance and differentiation      post-transcriptional regulation      epigenetic regulation     
Corresponding Author(s): CHEN Xin,Email:xchen32@jhu.edu   
Issue Date: 01 February 2013
 Cite this article:   
Iouri CHEPELEV,Xin CHEN. Alternative splicing switching in stem cell lineages[J]. Front Biol, 2013, 8(1): 50-59.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-012-1198-y
https://academic.hep.com.cn/fib/EN/Y2013/V8/I1/50
Fig.1  : A gene-centric view of the cellular information processing system (CIPS), see text for detailed explanation. : An example of applying the cellular information processing system (CIPS) framework to explain stem cell self-renewal and pluripotency. A multitude scenario can be used to explain how AS of pre-mRNAs can contribute to self-renewal and maintance of multipotency/pluripotency of stem cells, as well as their cellular differentiation. Some possible scenarios are shown here: the general pluripotency factors can modulate the activity of RBPs which regulate pre-mRNA splicing. Additionally, the pluripotency factors can affect splicing indirectly by changing the chromatin template of the corresponding genes. The dotted line coming out from the “pre-mRNA” rectangle symbolizes a particular isoform, which is not produced by the splicing process. An isoform produced by the splicing process may still be filtered out by a microRNA filter as depicted by the dotted line coming out from the filter. The production of the protein that promotes cellular differentiation is thus inhibited. Instead, the protein that promotes self-renewal and maintains pluripotency is produced. See and examples in the text. Abbreviations: TF-transcription factor; RBP-RNA binding protein; NMD-nonsense mediated decay.
1 Allemand E, Batsché E, Muchardt C (2008). Splicing, transcription, and chromatin: a ménage à trois. Curr Opin Genet Dev , 18(2): 145-151
doi: 10.1016/j.gde.2008.01.006 pmid:18372167
2 Alló M, Buggiano V, Fededa J P, Petrillo E, Schor I, de la Mata M, Agirre E, Plass M, Eyras E, Elela S A, Klinck R, Chabot B, Kornblihtt A R (2009). Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nat Struct Mol Biol , 16(7): 717-724
doi: 10.1038/nsmb.1620 pmid:19543290
3 Atlasi Y, Mowla S J, Ziaee S A, Gokhale P J, Andrews P W (2008). OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells , 26(12): 3068-3074
doi: 10.1634/stemcells.2008-0530 pmid:18787205
4 Azuara V, Perry P, Sauer S, Spivakov M, J?rgensen H F, John R M, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher A G (2006). Chromatin signatures of pluripotent cell lines. Nat Cell Biol , 8(5): 532-538
doi: 10.1038/ncb1403 pmid:16570078
5 Barash Y, Calarco J A, Gao W, Pan Q, Wang X, Shai O, Blencowe B J, Frey B J (2010). Deciphering the splicing code. Nature , 465(7294): 53-59
doi: 10.1038/nature09000 pmid:20445623
6 Barski A, Cuddapah S, Cui K, Roh T Y, Schones D E, Wang Z, Wei G, Chepelev I, Zhao K (2007). High-resolution profiling of histone methylations in the human genome. Cell , 129(4): 823-837
doi: 10.1016/j.cell.2007.05.009 pmid:17512414
7 Bernstein B E, Mikkelsen T S, Xie X, Kamal M, Huebert D J, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber S L, Lander E S (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell , 125(2): 315-326
doi: 10.1016/j.cell.2006.02.041 pmid:16630819
8 Bland C S, Cooper T A (2007). Micromanaging alternative splicing during muscle differentiation. Dev Cell , 12(2): 171-172
doi: 10.1016/j.devcel.2007.01.014 pmid:17276332
9 Bland C S, Wang E T, Vu A, David M P, Castle J C, Johnson J M, Burge C B, Cooper T A (2010). Global regulation of alternative splicing during myogenic differentiation. Nucleic Acids Res , 38(21): 7651-7664
doi: 10.1093/nar/gkq614 pmid:20634200
10 Boutz P L, Chawla G, Stoilov P, Black D L (2007a). MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev , 21(1): 71-84
doi: 10.1101/gad.1500707 pmid:17210790
11 Boutz P L, Stoilov P, Li Q, Lin C H, Chawla G, Ostrow K, Shiue L, Ares M Jr, Black D L (2007b). A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev , 21(13): 1636-1652
doi: 10.1101/gad.1558107 pmid:17606642
12 Boyer L A, Lee T I, Cole M F, Johnstone S E, Levine S S, Zucker J P, Guenther M G, Kumar R M, Murray H L, Jenner R G, Gifford D K, Melton D A, Jaenisch R, Young R A (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell , 122(6): 947-956
doi: 10.1016/j.cell.2005.08.020 pmid:16153702
13 Boyer L A, Mathur D, Jaenisch R (2006a). Molecular control of pluripotency. Curr Opin Genet Dev , 16(5): 455-462
doi: 10.1016/j.gde.2006.08.009 pmid:16920351
14 Boyer L A, Plath K, Zeitlinger J, Brambrink T, Medeiros L A, Lee T I, Levine S S, Wernig M, Tajonar A, Ray M K, Bell G W, Otte A P, Vidal M, Gifford D K, Young R A, Jaenisch R (2006b). Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature , 441(7091): 349-353
doi: 10.1038/nature04733 pmid:16625203
15 Chawla G, Lin C H, Han A, Shiue L, Ares M Jr, Black D L (2009). Sam68 regulates a set of alternatively spliced exons during neurogenesis. Mol Cell Biol , 29(1): 201-213
doi: 10.1128/MCB.01349-08 pmid:18936165
16 Chen X (2008). Stem cells: what can we learn from flies? Fly (Austin) , 2(1): 19-28
pmid:18820440
17 Cover T M, Thomas J A (1991). Elements of information theory, 1st Edition. New York: Wiley-Interscience
18 Das S,Jena S,Levasseur D N (2011). Alternative splicing produces nanog protein variants with different capacities for self-renewal and pluripotency in embryonic stem cells. J Biol Chem , 286(49):42690-42703
19 Eun S H, Gan Q, Chen X (2010). Epigenetic regulation of germ cell differentiation. Curr Opin Cell Biol , 22(6): 737-743
doi: 10.1016/j.ceb.2010.09.004 pmid:20951019
20 Evans M J, Kaufman M H (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature , 292(5819): 154-156
doi: 10.1038/292154a0 pmid:7242681
21 Fuller M T, Spradling A C (2007). Male and female Drosophila germline stem cells: two versions of immortality. Science , 316(5823): 402-404
doi: 10.1126/science.1140861 pmid:17446390
22 Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O’Hanlon D, Sung H K, Alvarez M, Talukder S, Pan Q, Mazzoni E O, Nedelec S, Wichterle H, Woltjen K, Hughes T R, Zandstra P W, Nagy A, Wrana J L, Blencowe B J (2011). An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell , 147(1): 132-146
doi: 10.1016/j.cell.2011.08.023 pmid:21924763
23 Gan Q, Chepelev I, Wei G, Tarayrah L, Cui K, Zhao K, Chen X (2010). Dynamic regulation of alternative splicing and chromatin structure in Drosophila gonads revealed by RNA-seq. Cell Res , 20(7): 763-783
doi: 10.1038/cr.2010.64 pmid:20440302
24 Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason M J, Heidersbach A, Ramalho-Santos J, McManus M T, Plath K, Meshorer E, Ramalho-Santos M (2009). Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature , 460(7257): 863-868
pmid:19587682
25 Guan K, Nayernia K, Maier L S, Wagner S, Dressel R, Lee J H, Nolte J, Wolf F, Li M, Engel W, Hasenfuss G (2006). Pluripotency of spermatogonial stem cells from adult mouse testis. Nature , 440(7088): 1199-1203
doi: 10.1038/nature04697 pmid:16565704
26 Guenther M G, Levine S S, Boyer L A, Jaenisch R, Young R A (2007). A chromatin landmark and transcription initiation at most promoters in human cells. Cell , 130(1): 77-88
doi: 10.1016/j.cell.2007.05.042 pmid:17632057
27 Jurica M S, Moore M J (2003). Pre-mRNA splicing: awash in a sea of proteins. Mol Cell , 12(1): 5-14
doi: 10.1016/S1097-2765(03)00270-3 pmid:12887888
28 Kanatsu-Shinohara M, Inoue K, Lee J, Yoshimoto M, Ogonuki N, Miki H, Baba S, Kato T, Kazuki Y, Toyokuni S, Toyoshima M, Niwa O, Oshimura M, Heike T, Nakahata T, Ishino F, Ogura A, Shinohara T (2004). Generation of pluripotent stem cells from neonatal mouse testis. Cell , 119(7): 1001-1012
doi: 10.1016/j.cell.2004.11.011 pmid:15620358
29 Kim J, Chu J, Shen X, Wang J, Orkin S H (2008). An extended transcriptional network for pluripotency of embryonic stem cells. Cell , 132(6): 1049-1061
doi: 10.1016/j.cell.2008.02.039 pmid:18358816
30 Kunarso G, Wong K Y, Stanton L W, Lipovich L (2008). Detailed characterization of the mouse embryonic stem cell transcriptome reveals novel genes and intergenic splicing associated with pluripotency. BMC Genomics , 9(1): 155
doi: 10.1186/1471-2164-9-155 pmid:18400104
31 Lareau L F, Inada M, Green R E, Wengrod J C, Brenner S E (2007). Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements. Nature , 446(7138): 926-929
doi: 10.1038/nature05676 pmid:17361132
32 Lee J, Kim H K, Rho J Y, Han Y M, Kim J (2006a). The human OCT-4 isoforms differ in their ability to confer self-renewal. J Biol Chem , 281(44): 33554-33565
doi: 10.1074/jbc.M603937200 pmid:16951404
33 Lee T I, Jenner R G, Boyer L A, Guenther M G, Levine S S, Kumar R M, Chevalier B, Johnstone S E, Cole M F, Isono K, Koseki H, Fuchikami T, Abe K, Murray H L, Zucker J P, Yuan B, Bell G W, Herbolsheimer E, Hannett N M, Sun K, Odom D T, Otte A P, Volkert T L, Bartel D P, Melton D A, Gifford D K, Jaenisch R, Young R A (2006b). Control of developmental regulators by Polycomb in human embryonic stem cells. Cell , 125(2): 301-313
doi: 10.1016/j.cell.2006.02.043 pmid:16630818
34 Lemischka I R, Pritsker M (2006). Alternative splicing increases complexity of stem cell transcriptome. Cell Cycle , 5(4): 347-351
doi: 10.4161/cc.5.4.2424 pmid:16479168
35 Loh Y H, Wu Q, Chew J L, Vega V B, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, Wong K Y, Sung K W, Lee C W, Zhao X D, Chiu K P, Lipovich L, Kuznetsov V A, Robson P, Stanton L W, Wei C L, Ruan Y, Lim B, Ng H H (2006). The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet , 38(4): 431-440
doi: 10.1038/ng1760 pmid:16518401
36 Losick V P, Morris L X, Fox D T, Spradling A (2011). Drosophila stem cell niches: a decade of discovery suggests a unified view of stem cell regulation. Dev Cell , 21(1): 159-171
doi: 10.1016/j.devcel.2011.06.018 pmid:21763616
37 Luco R F, Allo M, Schor I E, Kornblihtt A R, Misteli T (2011). Epigenetics in alternative pre-mRNA splicing. Cell , 144(1): 16-26
doi: 10.1016/j.cell.2010.11.056 pmid:21215366
38 Luco R F, Misteli T (2011). More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation. Curr Opin Genet Dev , 21(4): 366-372
doi: 10.1016/j.gde.2011.03.004 pmid:21497503
39 Luco R F, Pan Q, Tominaga K, Blencowe B J, Pereira-Smith O M, Misteli T (2010). Regulation of alternative splicing by histone modifications. Science , 327(5968): 996-1000
doi: 10.1126/science.1184208 pmid:20133523
40 Martin G R (1981). Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA , 78(12): 7634-7638
doi: 10.1073/pnas.78.12.7634 pmid:6950406
41 Mayshar Y, Rom E, Chumakov I, Kronman A, Yayon A, Benvenisty N (2008). Fibroblast growth factor 4 and its novel splice isoform have opposing effects on the maintenance of human embryonic stem cell self-renewal. Stem Cells , 26(3): 767-774
doi: 10.1634/stemcells.2007-1037 pmid:18192227
42 Mikkelsen T S, Ku M, Jaffe D B, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim T K, Koche R P, Lee W, Mendenhall E, O’Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander E S, Bernstein B E (2007). Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature , 448(7153): 553-560
doi: 10.1038/nature06008 pmid:17603471
43 Molnár A, Georgopoulos K (1994). The Ikaros gene encodes a family of functionally diverse zinc finger DNA-binding proteins. Mol Cell Biol , 14(12): 8292-8303
pmid:7969165
44 Morrison S J, Kimble J (2006). Asymmetric and symmetric stem-cell divisions in development and cancer. Nature , 441(7097): 1068-1074
doi: 10.1038/nature04956 pmid:16810241
45 Morrison S J, Spradling A C (2008). Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell , 132(4): 598-611
doi: 10.1016/j.cell.2008.01.038 pmid:18295578
46 Mu?oz M J, Pérez Santangelo M S, Paronetto M P, de la Mata M, Pelisch F, Boireau S, Glover-Cutter K, Ben-Dov C, Blaustein M, Lozano J J, Bird G, Bentley D, Bertrand E, Kornblihtt A R (2009). DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell , 137(4): 708-720
doi: 10.1016/j.cell.2009.03.010 pmid:19450518
47 Nelles D A, Yeo G W (2010). Alternative splicing in stem cell self-renewal and diferentiation. Adv Exp Med Biol , 695: 92-104
doi: 10.1007/978-1-4419-7037-4_7 pmid:21222201
48 Ni J Z, Grate L, Donohue J P, Preston C, Nobida N, O’Brien G, Shiue L, Clark T A, Blume J E, Ares M Jr (2007). Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. Genes Dev , 21(6): 708-718
doi: 10.1101/gad.1525507 pmid:17369403
49 Park I H, Zhao R, West J A, Yabuuchi A, Huo H, Ince T A, Lerou P H, Lensch M W, Daley G Q (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature , 451(7175): 141-146
doi: 10.1038/nature06534 pmid:18157115
50 Pritsker M, Doniger T T, Kramer L C, Westcot S E, Lemischka I R (2005). Diversification of stem cell molecular repertoire by alternative splicing. Proc Natl Acad Sci USA , 102(40): 14290-14295
doi: 10.1073/pnas.0502132102 pmid:16183747
51 Rao S, Zhen S, Roumiantsev S, McDonald L T, Yuan G C, Orkin S H (2010). Differential roles of Sall4 isoforms in embryonic stem cell pluripotency. Mol Cell Biol , 30(22): 5364-5380
doi: 10.1128/MCB.00419-10 pmid:20837710
52 Richard S, Torabi N, Franco G V, Tremblay G A, Chen T, Vogel G, Morel M, Cléroux P, Forget-Richard A, Komarova S, Tremblay M L, Li W, Li A, Gao Y J, Henderson J E (2005). Ablation of the Sam68 RNA binding protein protects mice from age-related bone loss. PLoS Genet , 1(6): e74
doi: 10.1371/journal.pgen.0010074 pmid:16362077
53 Ritchie W, Granjeaud S, Puthier D, Gautheret D (2008). Entropy measures quantify global splicing disorders in cancer. PLOS Comput Biol , 4(3): e1000011
doi: 10.1371/journal.pcbi.1000011 pmid:18369415
54 Rossi D J, Jamieson C H, Weissman I L (2008). Stems cells and the pathways to aging and cancer. Cell , 132(4): 681-696
doi: 10.1016/j.cell.2008.01.036 pmid:18295583
55 Salomonis N, Nelson B, Vranizan K, Pico A R, Hanspers K, Kuchinsky A, Ta L, Mercola M, Conklin B R (2009). Alternative splicing in the differentiation of human embryonic stem cells into cardiac precursors. PLOS Comput Biol , 5(11): e1000553
doi: 10.1371/journal.pcbi.1000553 pmid:19893621
56 Salomonis N, Schlieve C R, Pereira L, Wahlquist C, Colas A, Zambon A C, Vranizan K, Spindler M J, Pico A R, Cline M S, Clark T A, Williams A, Blume J E, Samal E, Mercola M, Merrill B J, Conklin B R (2010). Alternative splicing regulates mouse embryonic stem cell pluripotency and differentiation. Proc Natl Acad Sci USA , 107(23): 10514-10519
doi: 10.1073/pnas.0912260107 pmid:20498046
57 Schor I E, Rascovan N, Pelisch F, Alló M, Kornblihtt A R (2009). Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc Natl Acad Sci USA , 106(11): 4325-4330
doi: 10.1073/pnas.0810666106 pmid:19251664
58 Schwartz S, Ast G (2010). Chromatin density and splicing destiny: on the cross-talk between chromatin structure and splicing. EMBO J , 29(10): 1629-1636
doi: 10.1038/emboj.2010.71 pmid:20407423
59 Schwartz S, Meshorer E, Ast G (2009). Chromatin organization marks exon-intron structure. Nat Struct Mol Biol , 16(9): 990-995
doi: 10.1038/nsmb.1659 pmid:19684600
60 Shibayama M, Ohno S, Osaka T, Sakamoto R, Tokunaga A, Nakatake Y, Sato M, Yoshida N (2009). Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation. FEBS J , 276(22): 6658-6668
doi: 10.1111/j.1742-4658.2009.07380.x pmid:19843185
61 Shukla S, Kavak E, Gregory M, Imashimizu M, Shutinoski B, Kashlev M, Oberdoerffer P, Sandberg R, Oberdoerffer S (2011). CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature , 479(7371): 74-79
doi: 10.1038/nature10442 pmid:21964334
62 Sims R J 3rd, Millhouse S, Chen C F, Lewis B A, Erdjument-Bromage H, Tempst P, Manley J L, Reinberg D (2007). Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol Cell , 28(4): 665-676
doi: 10.1016/j.molcel.2007.11.010 pmid:18042460
63 Smith A G (2001). Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol , 17(1): 435-462
doi: 10.1146/annurev.cellbio.17.1.435 pmid:11687496
64 Stock J K, Giadrossi S, Casanova M, Brookes E, Vidal M, Koseki H, Brockdorff N, Fisher A G, Pombo A (2007). Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat Cell Biol , 9(12): 1428-1435
doi: 10.1038/ncb1663 pmid:18037880
65 Sultan M, Schulz M H, Richard H, Magen A, Klingenhoff A, Scherf M, Seifert M, Borodina T, Soldatov A, Parkhomchuk D, Schmidt D, O’Keeffe S, Haas S, Vingron M, Lehrach H, Yaspo M L (2008). A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science , 321(5891): 956-960
doi: 10.1126/science.1160342 pmid:18599741
66 Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell , 131(5): 861-872
doi: 10.1016/j.cell.2007.11.019 pmid:18035408
67 Takahashi K, Yamanaka S (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell , 126(4): 663-676
doi: 10.1016/j.cell.2006.07.024 pmid:16904174
68 Trapnell C, Williams B A, Pertea G, Mortazavi A, Kwan G, van Baren M J, Salzberg S L, Wold B J, Pachter L (2010). Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol , 28(5): 511-515
doi: 10.1038/nbt.1621 pmid:20436464
69 Wahl M C, Will C L, Lührmann R (2009). The spliceosome: design principles of a dynamic RNP machine. Cell , 136(4): 701-718
doi: 10.1016/j.cell.2009.02.009 pmid:19239890
70 Wang E T, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore S F, Schroth G P, Burge C B (2008). Alternative isoform regulation in human tissue transcriptomes. Nature , 456(7221): 470-476
doi: 10.1038/nature07509 pmid:18978772
71 Wang Z, Burge C B (2008). Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA , 14(5): 802-813
doi: 10.1261/rna.876308 pmid:18369186
72 Wu J Q, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S, Raha D, Egholm M, Lin H, Weissman S, Cui W, Gerstein M, Snyder M (2010). Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing. Proc Natl Acad Sci USA , 107(11): 5254-5259
doi: 10.1073/pnas.0914114107 pmid:20194744
73 Wu Q, Chen X, Zhang J, Loh Y H, Low T Y, Zhang W, Zhang W, Sze S K, Lim B, Ng H H (2006). Sall4 interacts with Nanog and co-occupies Nanog genomic sites in embryonic stem cells. J Biol Chem , 281(34): 24090-24094
doi: 10.1074/jbc.C600122200 pmid:16840789
74 Yamashita Y M, Yuan H, Cheng J, Hunt A J (2010). Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. Cold Spring Harb Perspect Biol , 2(1): a001313
doi: 10.1101/cshperspect.a001313 pmid:20182603
75 Yeo G W, Coufal N G, Liang T Y, Peng G E, Fu X D, Gage F H (2009). An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat Struct Mol Biol , 16(2): 130-137
doi: 10.1038/nsmb.1545 pmid:19136955
76 Yeo G W, Xu X, Liang T Y, Muotri A R, Carson C T, Coufal N G, Gage F H (2007). Alternative splicing events identified in human embryonic stem cells and neural progenitors. PLOS Comput Biol , 3(10): 1951-1967
doi: 10.1371/journal.pcbi.0030196 pmid:17967047
77 Yu J, Vodyanik M A, Smuga-Otto K, Antosiewicz-Bourget J, Frane J L, Tian S, Nie J, Jonsdottir G A, Ruotti V, Stewart R, Slukvin I I, Thomson J A (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science , 318(5858): 1917-1920
doi: 10.1126/science.1151526 pmid:18029452
78 Zhang C, Zhang Z, Castle J, Sun S, Johnson J, Krainer A R, Zhang M Q (2008). Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev , 22(18): 2550-2563
doi: 10.1101/gad.1703108 pmid:18794351
79 Zhou Q, Chipperfield H, Melton D A, Wong W H (2007). A gene regulatory network in mouse embryonic stem cells. Proc Natl Acad Sci USA , 104(42): 16438-16443
doi: 10.1073/pnas.0701014104 pmid:17940043
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