engineering-artificial-factors-to-specifically-manipulate-alternative

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

The processing of most eukaryotic RNAs is mediated by RNA Binding Proteins (RBPs) with modular configurations, including an RNA recognition module, which ...

Shanghai Institutes for Biological Sciences (SIBS)

&#x5DF2;&#x8BC1;&#x660E;&#x5728;&#x4EA7;&#x540E;&#x808C;&#x8089;&#x732A;&#x9AA8;&#x9AD3;&#x95F4;&#x5145;&#x8D28;&#x5E72;&#x7EC6;&#x80DE;&#x5206;&#x5316;&#x4E3A;&#x8102;&#x80AA;&#x7EC6;&#x80DE;&#x3002;&#x8FD9;&#x63D0;&#x9AD8;&#x4E86;&#x8102;&#x80AA;&#x7EC6;&#x80DE;&#x6570;&#x76EE;&#x548C;&#x8102;&#x8D28;&#x7684;&#x79EF;&#x7D2F;&#xFF0C;&#x5E76;&#x88AB;&#x8BA4;&#x4E3A;&#x662F;&#x808C;&#x5185;&#x8102;&#x80AA;&#x7684;&#x8D77;&#x6E90;&#x3002;&#x5728;&#x6B64;&#x7814;&#x7A76;&#x4E2D;&#xFF0C;&#x5BF9;&#x732A;&#x808C;&#x8089;&#x7EC4;&#x7EC7; (pMDSCs) &#x4ECE;&#x95F4;&#x5145;&#x8D28;&#x5E72;&#x7EC6;&#x80DE;&#x5411;&#x8102;&#x80AA;&#x7EC6;&#x80DE;&#x5206;&#x5316;&#x7684;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x548C;&#x7CBE;&#x6C28;&#x9178;&#x5F71;&#x54CD;&#x8C03;&#x67E5;&#x4E86;&#x4F53;&#x5916;&#x3002;&#x80DE;&#x5185;&#x7518;&#x6CB9;&#x4E09;&#x916F;&#x6C34;&#x5E73;&#x662F;&#x51CF;&#x5C11;&#x5916;&#x6E90;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x548C;&#x7CBE;&#x6C28;&#x9178;&#x7684;&#x8865;&#x5145;&#x6216;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x6297;&#x4F53;&#x7684;&#x589E;&#x52A0; &#xFF08;P &lt; 0.01&#xFF09;&#x3002;&#x7531;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x5728; pMDSCs &#x4E2D;&#x7684;&#x8102;&#x8D28;&#x79EF;&#x7D2F;&#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x51CF;&#x8F7B;&#x4E86;&#x7CBE;&#x6C28;&#x9178;&#x8865;&#x5145;&#x5242; (P &lt; 0.01&#xFF09;&#x3002;&#x6210;&#x8102;&#x8F6C;&#x5F55;&#x56E0;&#x5B50;&#x7684;&#x8868;&#x8FBE;&#x6A21;&#x5F0F;&#x663E;&#x793A;&#xFF0C;&#x5916;&#x6E90;&#x6027;&#x7684;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x6291;&#x5236; PPAR&gamma;2 &#x548C; aP2 &#x8868;&#x8FBE; (P &lt; 0.01)&#xFF0C;&#x800C;&#x5728;&#x8865;&#x5145;&#x7CBE;&#x6C28;&#x9178;&#x6216;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x6297;&#x4F53;&#x4FC3;&#x8FDB; ADD1 &#x8868;&#x8FBE;&#x5F0F; &#xFF08;P &lt; 0.01&#xFF09;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x52A0;&#x4E0A;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x86CB;&#x767D;&#x6216;&#x5355;&#x6297;&#x4F53;&#x76F8;&#x6BD4;&#xFF0C;ADD1 &#x548C; PPAR&delta; &#x8868;&#x8FBE;&#x4E86;&#x7531;&#x6B64;&#x63A8;&#x52A8;&#x7CBE;&#x6C28;&#x9178;&#x548C;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x7684;&#x7EC4;&#x5408; (P &lt; 0.01&#xFF09;&#xFF0C;&#x548C;&#x7CBE;&#x6C28;&#x9178;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x6297;&#x4F53;&#x7ED3;&#x5408;&#x4FC3;&#x8FDB; ADD1&#x3001; PPAR&delta;&#x3001; C/EBP&alpha;&#x3001; PPAR&gamma;2 &#x548C; LPL pMDSCs &#x4E2D;&#x7684;&#x8868;&#x8FBE;&#x5F0F; (P &lt; 0.05&#xFF09;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x8868;&#x660E;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x6291;&#x5236;&#x6210;&#x8102; pMDSCs &#x4E2D;, &#x548C;&#xFF0C;&#x8FD9;&#x53EF;&#x7F13;&#x89E3;&#x7531;&#x7CBE;&#x6C28;&#x9178;&#x8865;&#x5145;&#x5242;&#xFF0C;&#x81F3;&#x5C11;&#x5728;&#x90E8;&#x5206;&#xFF0C;&#x901A;&#x8FC7;&#x4FC3;&#x8FDB; ADD1 &#x548C; PPAR&delta; &#x7684;&#x8868;&#x8FBE;&#x3002;

&#x7531;&#x808C;&#x8089;&#x751F;&#x957F;&#x6291;&#x5236;&#x7D20;&#x5411;&#x8102;&#x80AA;&#x7EC6;&#x80DE;&#x5206;&#x5316;&#x7684;&#x6291;&#x5236;&#x4F5C;&#x7528;&#x88AB;&#x7F13;&#x89E3;&#x7CBE;&#x6C28;&#x9178;&#x8865;&#x5145;&#x5BF9;&#x732A;&#x808C;&#x6E90;&#x6027;&#x95F4;&#x5145;&#x8D28;&#x5E72;&#x7EC6;&#x80DE;&#x3002;

Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat. In this study, the effects of myostatin and arginine on adipogenic differentiation in mesenchymal stem cells derived from porcine muscle (pMDSCs) were investigated in vitro. Intracellular triglyceride levels were reduced by exogenous myostatin and increased by arginine supplementation or myostatin antibody (P<0.01). The inhibition of lipid accumulation by myostatin in pMDSCs was alleviated by arginine supplementation (P<0.01). Expression patterns of adipogenic transcription factors showed that exogenous myostatin suppressed PPARÎ³2 and aP2 expression (P<0.01), while supplemental arginine or myostatin antibody promoted ADD1 expression (P<0.01). Furthermore, compared with the addition of either myostatin protein or antibody alone, ADD1 and PPARÎ´ expression were promoted by the combination of arginine and myostatin (P<0.01), and arginine combined with myostatin antibody promoted the expression of ADD1, PPARÎ´, C/EBPÎ±, PPARÎ³2 and LPL in pMDSCs (P<0.05). These results suggest that myostatin inhibits adipogenesis in pMDSCs, and that this can be alleviated by arginine supplementation, at least in part, through promoting ADD1 and PPARÎ´ expression.

Inhibition of adipogenic differentiation by myostatin is alleviated by arginine supplementation in porcine-muscle-derived mesenchymal stem cells.

Porcines cellules souches m&eacute;senchymateuses dans le muscle postnatal ont &eacute;t&eacute; d&eacute;montr&eacute;es &agrave; se diff&eacute;rencier en adipocytes. Cela augmente l&#39;accumulation de nombre et lipides adipocytaire et est pens&eacute; pour &ecirc;tre &agrave; l&#39;origine du gras intramusculaire. Dans cette &eacute;tude, les effets de la myostatine et arginine sur la diff&eacute;renciation adipocytaire dans les cellules souches m&eacute;senchymateuses d&eacute;riv&eacute;es de muscle de porc (pMDSCs) ont &eacute;t&eacute; &eacute;tudi&eacute;s in vitro. Intracellulaire de triglyc&eacute;rides ont &eacute;t&eacute; r&eacute;duits de myostatine exog&egrave;ne et augment&eacute;s d&#39;anticorps de myostatine ou de la suppl&eacute;mentation en arginine (P &lt; 0,01). L&#39;inhibition de l&#39;accumulation de lipides de la myostatine dans pMDSCs a &eacute;t&eacute; att&eacute;nu&eacute;e par la suppl&eacute;mentation en arginine (P &lt; 0,01). Profils d&#39;expression des facteurs de transcription adipocytaire a montr&eacute; que myostatine exog&egrave;ne supprim&eacute; l&#39;expression PPAR&gamma;2 et aP2 (P &lt; 0,01), tandis que des anticorps arginine ou de la myostatine supplemental promu ADD1 expression (P &lt; 0,01). En outre, par rapport &agrave; l&#39;addition de myostatine prot&eacute;ines ou anticorps seul, expression ADD1 et PPAR&delta; ont &eacute;t&eacute; promus par la combinaison d&#39;arginine et de la myostatine (P &lt; 0,01), et de l&#39;arginine combin&eacute;e avec les anticorps de la myostatine favoris&eacute; l&#39;expression de ADD1, PPAR&delta;, C/EBP&alpha;, PPAR&gamma;2 et LPL dans pMDSCs (P &lt; 0,05). Ces r&eacute;sultats sugg&egrave;rent que myostatine inhibe l&#39;adipogen&egrave;se dans pMDSCs, et que cela peut &ecirc;tre all&eacute;g&eacute; par la suppl&eacute;mentation en arginine, au moins en partie, par la promotion d&#39;expression ADD1 et PPAR&delta;.

L&#39;inhibition de la diff&eacute;renciation adipocytaire de myostatine est att&eacute;nu&eacute;e par la suppl&eacute;mentation en arginine dans porcin-muscle-d&eacute;riv&eacute;es des cellules souches m&eacute;senchymateuses.

Porcine mesenchymaler Stammzellen in postnatale Muskel wurden nachgewiesen, um in Adipozyten zu unterscheiden. Dies erh&ouml;ht die Adipozyt Anzahl und Lipid-Anh&auml;ufung und ist vermutlich der Ursprung der intramuskul&auml;re Fett. In dieser Studie wurden die Auswirkungen von Myostatin und Arginin auf Adipogenic Differenzierung mesenchymaler Stammzellen aus Schweinen Muskel (pMDSCs) in-vitro untersucht. Intrazellul&auml;re Triglyzeride waren durch exogene Myostatin reduziert und stieg um Arginin-Supplementierung oder Myostatin-Antik&ouml;rper (P &lt; 0,01). Die Hemmung der Lipid-Anh&auml;ufung von Myostatin in pMDSCs wurde durch Arginin &uuml;berwinden (P &lt; 0,01). Ausdrucksmuster der Transkriptionsfaktoren Adipogenic zeigte, dass exogene Myostatin unterdr&uuml;ckt Ausdruck PPAR&gamma;2 und aP2 (P &lt; 0.01), w&auml;hrend zus&auml;tzliche Arginin oder Myostatin Antik&ouml;rper ADD1 Ausdruck gef&ouml;rdert (P &lt; 0,01). Dar&uuml;ber hinaus im Vergleich mit dem Zusatz von Myostatin-Protein oder Antik&ouml;rper allein, durch die Kombination von Arginin und Myostatin ADD1 und PPAR&delta; Ausdruck Aufsteiger (P &lt; 0.01), und Arginin in Kombination mit Myostatin Antik&ouml;rper bef&ouml;rdert den Ausdruck ADD1, PPAR&delta;, C/EBP&alpha;, PPAR&gamma;2 und LPL in pMDSCs (P &lt; 0,05). Diese Ergebnisse legen nahe, dass Myostatin hemmt Estrogenen in pMDSCs, und dass dies kann gelindert werden durch Arginin, zumindest teilweise, durch F&ouml;rderung der ADD1 und PPAR&delta; Ausdruck.

Hemmung der Adipogenic Differenzierung von Myostatin ist von Arginin in Schweinen Muskel-mesenchymale Stammzellen gemildert.

Porcine cellule staminali mesenchimali nel muscolo postnatale sono state dimostrate a differenziarsi in adipociti. Questo aumenta l&#39;accumulo di numero e lipidico degli adipociti ed &egrave; pensato per essere l&#39;origine di grasso intramuscolare. In questo studio, gli effetti della miostatina e arginina su adipogenic differenziazione in cellule staminali mesenchimali derivate dal muscolo suina (pMDSCs) sono stati studiati in vitro. I livelli di trigliceridi intracellulari sono stati ridotti di miostatina esogeno e aumentati dall&#39;anticorpo supplementazione o miostatina arginina (P &lt; 0,01). L&#39;inibizione di accumulo dei lipidi di miostatina in pMDSCs &egrave; stato alleviato dalla supplementazione di arginina (P &lt; 0,01). Pattern di espressione dei fattori di trascrizione adipogenic ha mostrato quello esogeno miostatina soppressa espressione PPAR&gamma;2 e aP2 (P &lt; 0,01), mentre l&#39;anticorpo supplementare di arginina o miostatina promosso ADD1 espressione (P &lt; 0,01). Inoltre, confrontato con l&#39;aggiunta della proteina miostatina o anticorpo da solo, espressione di ADD1 e PPAR&delta; sono stati promossi dalla combinazione di arginina e miostatina (P &lt; 0.01), e arginina, combinato con l&#39;anticorpo miostatina promosso l&#39;espressione di ADD1, PPAR&delta;, C/EBP&alpha;, PPAR&gamma;2 e LPL in pMDSCs (P &lt; 0,05). Questi risultati suggeriscono che inibisce la miostatina adipogenesi in pMDSCs, e che questo pu&ograve; essere alleviato dalla supplementazione di arginina, almeno in parte, attraverso la promozione di ADD1 e PPAR&delta; espressione.

L&#39;inibizione della differenziazione adipogenic di miostatina &egrave; alleviato dalla supplementazione di arginina nel porcino-muscolo-derivate le cellule staminali mesenchimali.

&#x30D6;&#x30BF;&#x5E79;&#x7D30;&#x80DE;&#x751F;&#x5F8C;&#x7B4B;&#x306B;&#x304A;&#x3051;&#x308B;&#x8102;&#x80AA;&#x7D30;&#x80DE;&#x306B;&#x533A;&#x5225;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x5B9F;&#x8A3C;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x306F;&#x3001;&#x8102;&#x80AA;&#x7D30;&#x80DE;&#x6570;&#x304A;&#x3088;&#x3073;&#x8102;&#x8CEA;&#x84C4;&#x7A4D;&#x3092;&#x9AD8;&#x3081;&#x3001;&#x7B4B;&#x8089;&#x3001;&#x8102;&#x80AA;&#x306E;&#x8D77;&#x6E90;&#x3068;&#x8003;&#x3048;&#x3089;&#x308C;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;, &#x30D6;&#x30BF;&#x7B4B;&#x8089; (pMDSCs) &#x7531;&#x6765;&#x9593;&#x8449;&#x7CFB;&#x5E79;&#x7D30;&#x80DE;&#x306E;&#x8102;&#x80AA;&#x5F62;&#x6210;&#x5206;&#x5316;&#x306B;&#x53CA;&#x307C;&#x3059;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x3068;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x306E; in vitro &#x3067;&#x8ABF;&#x3079;&#x305F;&#x3002;&#x7D30;&#x80DE;&#x5185;&#x306E;&#x30C8;&#x30EA;&#x30B0;&#x30EA;&#x30BB;&#x30EA;&#x30C9;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x3060;&#x3063;&#x305F;&#x306B;&#x3088;&#x308B;&#x5916;&#x56E0;&#x6027;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x3092;&#x77ED;&#x7E2E;&#x3057;&#x3001;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x88DC;&#x5145;&#x307E;&#x305F;&#x306F;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x6297;&#x4F53;&#x306B;&#x3088;&#x3063;&#x3066;&#x5897;&#x52A0;&#x3057;&#x305F; &#xFF08;P &lt; 0.01)&#x3002;PMDSCs &#x306B;&#x304A;&#x3051;&#x308B;&#x30DE;&#x30A4;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x306B;&#x3088;&#x308B;&#x8102;&#x8CEA;&#x84C4;&#x7A4D;&#x306E;&#x6291;&#x5236;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x88DC;&#x5145;&#x306B;&#x3088;&#x3063;&#x3066;&#x8EFD;&#x6E1B;&#x3059;&#x308B; (P &lt; 0.01)&#x3002;&#x8102;&#x80AA;&#x5206;&#x5316;&#x306E;&#x8EE2;&#x5199;&#x56E0;&#x5B50;&#x306E;&#x767A;&#x73FE;&#x30D1;&#x30BF;&#x30FC;&#x30F3;&#x3092;&#x793A;&#x3057;&#x305F;&#x305D;&#x306E;&#x5916;&#x56E0;&#x6027;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x6291;&#x5236; PPAR&gamma;2 &#x3068; aP2 &#x5F0F; (P &lt; 0.01)&#x3001;&#x88DC;&#x8DB3;&#x7684;&#x306A;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x307E;&#x305F;&#x306F;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x6297;&#x4F53; ADD1 &#x5F0F;&#x63A8;&#x9032;&#x4E2D; (P &lt; 0.01)&#x3002;ADD1 &#x3068; PPAR&delta; &#x5F0F;&#x306F;&#x307E;&#x305F;&#x3001;&#x3054;&#x308D;&#x304B;&#x3089;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x3068;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x306E;&#x7D44;&#x307F;&#x5408;&#x308F;&#x305B;&#x306B;&#x3088;&#x3063;&#x3066;&#x4FC3;&#x9032;&#x3055;&#x308C;&#x305F;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x86CB;&#x767D;&#x8CEA;&#x304B;&#x6297;&#x4F53;&#x5358;&#x72EC;&#x6DFB;&#x52A0;&#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066;&#x3001;(P &lt; 0.01)&#x3001;&#x304A;&#x3088;&#x3073;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x6297;&#x4F53;&#x3068;&#x7D50;&#x5408;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x6607;&#x683C; ADD1&#x3001;PPAR&delta; C/EBP&alpha;&#x3001;PPAR&gamma;2&#x3001;LPL &#x306E;&#x5F0F; pMDSCs &#x3067; (P &lt; 0.05)&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x7D50;&#x679C;&#x304B;&#x3089;&#x793A;&#x5506;&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x963B;&#x5BB3; t3-l1 pMDSCs &#x3068;&#x306F;&#x3001;&#x3053;&#x306E;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x88DC;&#x5145;&#x306B;&#x3088;&#x3063;&#x3066;&#x5C11;&#x306A;&#x304F;&#x3068;&#x3082;&#x4E00;&#x90E8; ADD1 &#x3068; PPAR&delta; &#x5F0F;&#x306E;&#x63A8;&#x9032;&#x3092;&#x901A;&#x3058;&#x3066;&#x3067;&#x8EFD;&#x6E1B;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;

&#x30DF;&#x30AA;&#x30B9;&#x30BF;&#x30C1;&#x30F3;&#x306B;&#x3088;&#x3063;&#x3066;&#x7B4B;&#x8089;&#x5185;&#x8102;&#x80AA;&#x7D30;&#x80DE;&#x5206;&#x5316;&#x6291;&#x5236;&#x30A2;&#x30EB;&#x30AE;&#x30CB;&#x30F3;&#x88DC;&#x5145;&#x8C5A;&#x7B4B;&#x8089;&#x7531;&#x6765;&#x9593;&#x8449;&#x7CFB;&#x5E79;&#x7D30;&#x80DE;&#x306B;&#x3088;&#x3063;&#x3066;&#x7DE9;&#x548C;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;

&#xC0B0; &#xD6C4; &#xADFC;&#xC721;&#xC5D0;&#xC11C; &#xB3FC;&#xC9C0; &#xC911;&#xAC04; &#xC5FD; &#xC904;&#xAE30; &#xC138;&#xD3EC; adipocytes&#xB85C; &#xCC28;&#xBCC4;&#xD654; &#xD558;&#xB294; &#xB370; &#xC785;&#xC99D; &#xB418;&#xC5B4; &#xC788;&#xB2E4;. &#xCCB4;&#xD615; &#xC218; &#xBC0F; &#xC9C0;&#xC9C8; &#xCD95;&#xC801; &#xB298;&#xC5B4;&#xB098;&#xACE0; &#xADFC;&#xC721; &#xC9C0;&#xBC29; &#xAE30;&#xC6D0; &#xB420; &#xAC83;&#xC73C;&#xB85C; &#xC0DD;&#xAC01; &#xB429;&#xB2C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C; &#xB3FC;&#xC9C0; &#xADFC;&#xC721; (pMDSCs)&#xC5D0;&#xC11C; &#xD30C;&#xC0DD; &#xB41C; &#xC911;&#xAC04; &#xC5FD; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; &#xBD84;&#xD654; adipogenic myostatin &#xC544;&#xB974;&#xAE30;&#xB2CC;&#xC758; &#xD6A8;&#xACFC; &#xCCB4; &#xC678; &#xC870;&#xC0AC; &#xD588;&#xB2E4;. &#xC138;&#xD3EC;&#xB0B4; triglyceride &#xB808;&#xBCA8; exogenous myostatin &#xAC10;&#xC18C; &#xB418;&#xC5C8;&#xACE0; &#xC544;&#xB974;&#xAE30;&#xB2CC; &#xBCF4;&#xCDA9; &#xB610;&#xB294; myostatin &#xD56D; &#xCCB4; &#xC99D;&#xAC00; (P &lt; 0.01). &#xC544;&#xB974;&#xAE30;&#xB2CC; &#xBCF4;&#xCDA9; myostatin Pmdscs&#xC5D0; &#xC758;&#xD574; &#xC9C0;&#xC9C8; &#xCD95;&#xC801; &#xC5B5;&#xC81C; &#xC644;&#xD654; &#xB418;&#xC5C8;&#xB2E4; (P &lt; 0.01). &#xC2DD; &#xD328;&#xD134; adipogenic &#xB179;&#xC74C; &#xBC29;&#xC1A1; &#xC694;&#xC778;&#xC758; &#xADF8; exogenous myostatin Ppar&gamma;2&#xC640; aP2 &#xC2DD; &#xC5B5;&#xC81C; &#xBCF4;&#xC5EC;&#xC8FC;&#xC5C8;&#xB2E4; (P &lt; 0.01) &#xBCF4;&#xCDA9; arginine &#xB610;&#xB294; myostatin &#xD56D; &#xCCB4; &#xD504;&#xB85C; &#xBAA8;&#xC158; ADD1 &#xC2DD;&#xC740; &#xB3D9;&#xC548;, (P &lt; 0.01). &#xB610;&#xD55C;, myostatin &#xB2E8;&#xBC31;&#xC9C8; &#xB610;&#xB294; &#xD56D; &#xCCB4; &#xD63C;&#xC790; &#xCD94;&#xAC00; &#xBE44;&#xD574; add1&#xACFC; PPAR&delta; &#xC2DD; &#xC2B9;&#xC9C4; &#xD588;&#xB2E4; &#xC544;&#xB974;&#xAE30;&#xB2CC;&#xACFC; myostatin&#xC758; &#xC870;&#xD569;&#xC5D0; &#xC758;&#xD574; (P &lt; 0.01), &#xC544;&#xB974;&#xAE30;&#xB2CC; myostatin &#xD56D; &#xCCB4;&#xC640; &#xACB0;&#xD569; &#xD558; &#xC5EC; Pmdscs&#xC5D0;&#xC11C; ADD1, PPAR&delta;, C/EBP&alpha;, PPAR&gamma;2 &#xBC0F; LPL &#xC2DD; &#xC2B9;&#xC9C4; (P &lt; 0.05). &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4; myostatin &#xC5B5;&#xC81C;&#xC5D0; pMDSCs, adipogenesis &#xBC0F;&#xC774; &#xC644;&#xD654; &#xB420; &#xC218; &#xC788;&#xB2E4; &#xC544;&#xB974;&#xAE30;&#xB2CC; &#xBCF4;&#xCDA9; &#xD558; &#xC5EC; &#xC801;&#xC5B4;&#xB3C4; add1&#xACFC; PPAR&delta; &#xC2DD; &#xD64D;&#xBCF4;&#xB97C; &#xD1B5;&#xD574; &#xBD80;&#xBD84;&#xC5D0;&#xC11C;.

Myostatin &#xC5EC; adipogenic &#xBD84;&#xD654;&#xC758; &#xC5B5;&#xC81C;&#xB294; &#xC544;&#xB974;&#xAE30;&#xB2CC; &#xBCF4;&#xCDA9; &#xB3FC;&#xC9C0; &#xADFC;&#xC721; &#xC720;&#xB798; &#xC911;&#xAC04; &#xC5FD; &#xC904;&#xAE30; &#xC138;&#xD3EC;&#xC5D0; &#xC758;&#xD574; &#xC644;&#xD654; &#xB429;&#xB2C8;&#xB2E4;.

Las c&eacute;lulas madre mesenquimales porcinas en m&uacute;sculo postnatal se han demostrado para diferenciarse en adipocitos. Esto aumenta la acumulaci&oacute;n de n&uacute;mero y de los l&iacute;pidos de adipocitos y se cree que el origen de la grasa intramuscular. En este estudio se investigaron los efectos de la miostatina y arginina en adipogenic diferenciaci&oacute;n en c&eacute;lulas mesenquimales obtenidas de m&uacute;sculo porcino (pMDSCs) in vitro. Triglic&eacute;ridos intracelulares se redujo por miostatina ex&oacute;geno y aument&oacute; por anticuerpo suplementaci&oacute;n o miostatina arginina (P &lt; 0.01). La inhibici&oacute;n de la acumulaci&oacute;n de l&iacute;pidos de la miostatina en pMDSCs fue aliviada por la suplementaci&oacute;n con arginina (P &lt; 0.01). Patrones de expresi&oacute;n de factores de transcripci&oacute;n adipogenic demostraron que miostatina ex&oacute;geno suprime expresi&oacute;n PPAR&gamma;2 y aP2 (P &lt; 0.01), mientras que el anticuerpo suplementario de arginina o la miostatina promovido ADD1 expresi&oacute;n (P &lt; 0.01). Adem&aacute;s, en comparaci&oacute;n con la adici&oacute;n de la miostatina prote&iacute;nas o anticuerpos solo, expresi&oacute;n ADD1 y PPAR&delta; fueron promovidos por la combinaci&oacute;n de arginina y miostatina (P &lt; 0.01), y arginina combinada con el anticuerpo de la miostatina promueve la expresi&oacute;n de ADD1, PPAR&delta;, C/EBP&alpha;, PPAR&gamma;2 y LPL en pMDSCs (P &lt; 0.05). Estos resultados sugieren que miostatina inhibe la adipog&eacute;nesis en pMDSCs, y que esto puede ser aliviado por la suplementaci&oacute;n con arginina, al menos en parte, mediante el fomento de la expresi&oacute;n ADD1 y PPAR&delta;.

Inhibici&oacute;n de la diferenciaci&oacute;n adipogenic por miostatina es aliviada por suplementos de arginina en porcino-m&uacute;sculo-producidas por c&eacute;lulas madre mesenquimal.

Recently, increasing evidence supports that adult stem cells are the part of a natural system for tissue growth and repair. This study focused on the differences of mesenchymal stem cells from adult adipose (ADSCs), skeletal muscle (MDSCs) and fetal muscle (FMSCs) in biological characteristics, which is the key to cell therapy success. Stem cell antigen 1 (Sca-1) expression of MDSCs and FMSCs at passage 3 was two times more than that at passage 1 (P < 0.0001). After 28-day myogenic induction, higher expression levels of skeletal muscle-specific genes were observed in MDSCs than FMSCs (P < 0.01), and the lowest expression levels were demonstrated in ADSCs among three cells (P < 0.01). Besides, M-Cad and MyHC expressions in ADSCs were not detected by immunofluorescence or real-time quantitative PCR. Furthermore, after 14 days adipogenic induction, PPARγ2, LPL and aP2 mRNA expressions were higher in ADSCs vs. MDSCs (P < 0.01). Besides, MSCs from adult or fetal muscle expressed higher OCN and OPN than ADSCs after 28 days osteogenic induction (P < 0.01). Taken together, our results suggested that cell source and developmental stage had great impacts on biological properties of mesenchymal stem cells, and proper consideration of all the issues is necessary.

Comparative analysis of mesenchymal stem cells from adult mouse adipose, muscle, and fetal muscle.

In plants, microRNAs (miRNAs) are endogenous ~22 nt RNAs that play important regulatory roles in many aspects of plant biology, including metabolism, hormone response, epigenetic control of transposable elements, and stress response. Extensive studies of miRNAs have been performed in model plants such as rice and Arabidopsis thaliana. In maize, most miRNAs and their target genes were analyzed and identified by clearly different treatments, such as response to low nitrate, salt and drought stress. However, little is known about miRNAs involved in maize ear development. The objective of this study is to identify conserved and novel miRNAs and their target genes by combined small RNA and degradome sequencing at four inflorescence developmental stages.

Identification of miRNAs and their target genes in developing maize ears by combined small RNA and degradome sequencing.

Myostatin (Mstn) knockout mice exhibit large increases in skeletal muscle mass. However, relatively few of the genes that mediate or modify MSTN effects are known. In this study, we performed co-expression network analysis using whole transcriptome microarray data from MSTN-null and wild-type mice to identify genes involved in important biological processes and pathways related to skeletal muscle and adipose development. Genes differentially expressed between wild-type and MSTN-null mice were further analyzed for shared DNA motifs using DREME. Differentially expressed genes were identified at 13.5 d.p.c. during primary myogenesis and at d35 during postnatal muscle development, but not at 17.5 d.p.c. during secondary myogenesis. In total, 283 and 2034 genes were differentially expressed at 13.5 d.p.c. and d35, respectively. Over-represented transcription factor binding sites in differentially expressed genes included SMAD3, SP1, ZFP187, and PLAGL1. The use of regulatory (RIF) and phenotypic (PIF) impact factor and differential hubbing co-expression analyses identified both known and potentially novel regulators of skeletal muscle growth, including Apobec2, Atp2a2, and Mmp13 at d35 and Sox2, Tmsb4x, and Vdac1 at 13.5 d.p.c. Among the genes with the highest PIF scores were many fiber type specifying genes. The use of RIF, PIF, and differential hubbing analyses identified both known and potentially novel regulators of muscle development. These results provide new details of how MSTN may mediate transcriptional regulation as well as insight into novel regulators of MSTN signal transduction that merit further study regarding their physiological roles in muscle and adipose development.

Gene co-expression network analysis provides novel insights into myostatin regulation at three different mouse developmental timepoints.

The present study profiled and analyzed gene expression of the maize ear at four key developmental stages. Based on genome-wide profile analysis, we detected differential mRNA of maize genes. Some of the differentially expressed genes (DEGs) were predicted to be potential candidates of maize ear development. Several well-known genes were found with reported mutant analyses, such as, compact plant2 (ct2), zea AGAMOUS homolog1 (zag1), bearded ear (bde), and silky1 (si1). MicroRNAs such as microRNA156 were predicted to target genes involved in maize ear development. Antisense transcripts were widespread throughout all the four stages, and are suspected to play important roles in maize ear development. Thus, identification and characterization of important genes and regulators at all the four developmental stages will contribute to an improved understanding of the molecular mechanisms responsible for maize ear development.

Genome-wide comparative analysis of digital gene expression tag profiles during maize ear development.

The present study was carried out to investigate the prognostic factors in patients who received intra-arterial infusion for advanced pancreatic cancer. In addition, the detailed procedure of intra-arterial infusion chemotherapy was described. A total of 354 patients with advanced unresectable pancreatic adenocarcinoma were recruited from January 2012, to April 2015, at Zhongshan Hospital Fudan University, Shanghai, China. Demographic and clinic characteristics of the patients were extracted from electronic medical records. Restricted cubic spline was used to assess the nonliner regression between baseline CA19-9 value and overall survival. Kaplan-Meier analysis and Cox proportional hazard models were used to estimate the association between overall survival and clinical characteristics. Of all 354 included patients, 230 (65%) were male (male/female ratio = 1.8), and 72 (20%) patients were diagnosed with detectable distant metastases. Pretreatment CA19-9 value of patients with metastases was significantly higher as compared to those with locally advanced cancer (median: 922.30 vs 357.00 U/mL, P = 0.0090). Totally 274 patients completed 1 cycle of intra-arterial infusion, whereas 80 patients received 2 or more cycles of the chemotherapy. For all the 354 patients, median OS was 7.0 months (95% CI: 6.0, 8.0 months) with a 6-, 12-, and 18-month survival rate of 0.48, 0.28, and 0.18, respectively. The median OS of patients, who received 1 cycle of intra-arterial infusion therapy, was 6.0 months (95% CI: 5.0, 8.0 months), which was similar to 7.0 months (95% CI: 6.0, 9.0 months) in patients who received 2 or more cycles. Restricted cubic spline revealed the nonline association between baseline CA19-9 and prognosis. The Cox proportional hazard model showed that age, CA19-9 baseline, CA19-9 value, and tumor location were significantly associated with the OS. In conclusion, the gemcitabine-based RIAC presented a potential treatment method for advanced pancreatic adenocarcinoma. Young age, pretreatment CA19-9 value <1000 U/mL, and tumor located at the head of pancreas indicated better response to the regional intra-arterial chemotherapy and better overall survival.

Xuerong Yang

Key Laboratory of Computational Biology,
CAS-MPG Partner Institute for Computational Biology,
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology

Shanghai Institutes for Biological Sciences (SIBS)

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Xuerong Yang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Key Laboratory of Computational Biology,CAS-MPG Partner Institute for Computational Biology,Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology

Shanghai Institutes for Biological Sciences (SIBS)

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Key Laboratory of Computational Biology,
CAS-MPG Partner Institute for Computational Biology,
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology