<em>In Vitro</em> Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas

Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. ...

Beckman Research Institute of City of Hope

The Sno oncogene (Snoo or dSno in Drosophila) is a highly conserved protein and a well-established antagonist of Transforming Growth Factor-beta signaling in overexpression assays. However, analyses of Sno mutants in flies and mice have proven enigmatic in revealing developmental roles for Sno proteins. Thus, to identify developmental roles for dSno we first reconciled conflicting data on the lethality of dSno mutations. Then we conducted analyses of wing development in dSno loss of function genotypes. These studies revealed ectopic margin bristles and ectopic campaniform sensilla in the anterior compartment of the wing blade suggesting that dSno functions to antagonize Wingless (Wg) signaling. A subsequent series of gain of function analyses yielded the opposite phenotype (loss of bristles and sensilla) and further suggested that dSno antagonizes Wg signal transduction in target cells. To date Sno family proteins have not been reported to influence the Wg pathway during development in any species. Overall our data suggest that dSno functions as a tissue-specific component of the Wg signaling pathway with modest antagonistic activity under normal conditions but capable of blocking significant levels of extraneous Wg, a role that may be conserved in vertebrates.

The Sno oncogene antagonizes Wingless signaling during wing development in Drosophila.

It is well known that the Dpp signal transducer Mad is activated by phosphorylation at its carboxy-terminus. The role of phosphorylation on other regions of Mad is not as well understood. Here we report that the phosphorylation of Mad in the linker region by the Wg antagonist Zw3 (homolog of vertebrate Gsk3-β) regulates the development of sensory organs in the anterior-dorsal quadrant of the wing. Proneural expression of Mad-RNA interference (RNAi) or a Mad transgene with its Zw3/Gsk3-β phosphorylation sites mutated (MGM) generated wings with ectopic sensilla and chemosensory bristle duplications. Studies with pMad-Gsk (an antibody specific to Zw3/Gsk3-β-phosphorylated Mad) in larval wing disks revealed that this phosphorylation event is Wg dependent (via an unconventional mechanism), is restricted to anterior-dorsal sensory organ precursors (SOP) expressing Senseless (Sens), and is always co-expressed with the mitotic marker phospho-histone3. Quantitative analysis in both Mad-RNAi and MGM larval wing disks revealed a significant increase in the number of Sens SOP. We conclude that the phosphorylation of Mad by Zw3 functions to prevent the self-renewal of Sens SOP, perhaps facilitating their differentiation via asymmetric division. The conservation of Zw3/Gsk3-β phosphorylation sites in vertebrate homologs of Mad (Smads) suggests that this pathway, the first transforming growth factor β-independent role for any Smad protein, may be widely utilized for regulating mitosis during development.

Wg signaling via Zw3 and mad restricts self-renewal of sensory organ precursor cells in Drosophila.

&#x4F5C;&#x4E3A; morphogens &#x5206;&#x6CCC;&#x8F6C;&#x5316;&#x751F;&#x957F;&#x56E0;&#x5B50; &beta; (TGF&beta;) &#x86CB;&#x767D;&#x7684;&#x80FD;&#x529B;&#x51B3;&#x5B9A;&#x5176;&#x5F71;&#x54CD;&#x53D7;&#x4E25;&#x683C;&#x89C4;&#x7BA1;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x62A5;&#x544A;&#x6BCD;&#x7CFB;&#x4FC3;&#x8FDB;&#x8102;&#x80AA;&#x65B9;&#x9762; (&#x7D22;&#x65AF; &#xFF1B; &#x540C;&#x7CFB;&#x7269;&#x7684; USP9X/FAM) &#x662F;&#x6B63;&#x786E;&#x89E3;&#x91CA;&#x8BE5;&#x6A21;&#x5F0F;&#x7684;&#x80DA;&#x80CE;&#x80CC;&#x8179;&#x4FA7;&#x8F74;&#x5408;&#x5B50; &#xFF08;&#x6C11;&#x8FDB;&#x515A;&#xFF09; Decapentaplegic morphogen &#x6E10;&#x53D8;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x8868;&#x660E;&#x7D22;&#x65AF;&#x7684;&#x635F;&#x5931;&#x4F4E;&#x4E8E;&#x6240;&#x9700;&#x7684;&#x6700;&#x4F4E;&#x8DB3;&#x591F;&#x6C11;&#x8FDB;&#x515A;&#x4FE1;&#x53F7;&#x964D;&#x4F4E;&#x6D3B;&#x6027;&#x7684;&#x7F8E;&#x72C4;&#x4E9A; (Smad4 &#x7684;&#x540C;&#x7CFB;&#x7269;) &#x548C;&#x8FD9;&#x53EF;&#x80FD;&#x662F;&#x7531;&#x4E8E;&#x8FC7;&#x5EA6;&#x6CDB;&#x7D20;&#x5316;&#x5BF9;&#x7279;&#x5B9A;&#x7684;&#x8D56;&#x6C28;&#x9178;&#x3002;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x652F;&#x6301;&#x7EC6;&#x80DE;&#x54CD;&#x5E94;&#x7EA7;&#x522B; Smad4 &#x6CDB;&#x7D20;&#x5316;&#x7684; TGF&beta; &#x4FE1;&#x53F7;&#x7684;&#x63A7;&#x5236;&#x662F;&#x6240;&#x9700;&#x7684;&#x9002;&#x5F53;&#x6267;&#x884C; morphogen &#x6E10;&#x53D8;&#x7684;&#x5B88;&#x6052;&#x7684;&#x673A;&#x5236;&#x7684;&#x5047;&#x8BF4;&#x3002;

&#x7F8E;&#x72C4;&#x4E9A;/Smad4 &#x7684;&#x8102;&#x80AA;&#x65B9;&#x9762;&#x53BB;&#x8C03;&#x8282;&#x6C11;&#x8FDB;&#x515A; morphogen &#x6E10;&#x53D8;&#x7684;&#x89E3;&#x91CA;&#x3002;

The ability of secreted Transforming Growth Factor Î² (TGFÎ²) proteins to act as morphogens dictates that their influence be strictly regulated. Here, we report that maternally contributed fat facets (faf; a homolog of USP9X/FAM) is essential for proper interpretation of the zygotic Decapentaplegic (Dpp) morphogen gradient that patterns the embryonic dorsal-ventral axis. The data suggest that the loss of faf reduces the activity of Medea (a homolog of Smad4) below the minimum necessary for adequate Dpp signaling and that this is likely due to excessive ubiquitylation on a specific lysine. This study supports the hypothesis that the control of cellular responsiveness to TGFÎ² signals at the level of Smad4 ubiquitylation is a conserved mechanism required for proper implementation of a morphogen gradient.

Fat facets deubiquitylation of Medea/Smad4 modulates interpretation of a Dpp morphogen gradient.

La capacit&eacute; des prot&eacute;ines s&eacute;cr&eacute;t&eacute;es de &beta; (TGF&beta;) facteur de croissance transformant d&#39;agir comme morphog&egrave;nes dicte que leur influence soit strictement r&eacute;glement&eacute;. Nous rapportons ici, que des facettes fat maternellement contribu&eacute;s (faf; un homologue de USP9X/FAM) est essentielle pour une interpr&eacute;tation correcte du gradient autocatalytiques zygotique Decapentaplegic (Dpp) que les motifs de l&#39;axe embryonnaire de la dorsale-ventral. Les donn&eacute;es sugg&egrave;rent que la perte de la faf a r&eacute;duit l&#39;activit&eacute; de M&eacute;d&eacute;e (un homologue de Smad4) au-dessous du minimum n&eacute;cessaire pour la signalisation ad&eacute;quate de Dpp et que cela est probablement d&ucirc; &agrave; l&#39;ubiquitination excessive sur une lysine sp&eacute;cifique. Cette &eacute;tude confirme l&#39;hypoth&egrave;se que le contr&ocirc;le de la r&eacute;activit&eacute; cellulaire aux signaux TGF&beta; au niveau de l&#39;ubiquitination Smad4 est un m&eacute;canisme conserv&eacute; requis pour la bonne mise en &oelig;uvre d&#39;un gradient de capacit&eacute;s.

Facettes graisse deubiquitylation de M&eacute;d&eacute;e/Smad4 module interpr&eacute;tation d&#39;un gradient d&#39;autocatalytiques Dpp.

Die Handlungsf&auml;higkeit der sekretierten Proteine der Transforming Growth Factor-&beta; (TGF&beta;) als Morphogens schreibt vor, dass ihr Einfluss streng geregelt werden. Hier berichten wir, dass Maternal eingebrachte Fette Facetten (faf; eine homologe USP9X/FAM) ist wichtig f&uuml;r die richtige Auslegung der die zygotic Decapentaplegic (Dpp) Morphogen Steigung, die Anleitungen f&uuml;r die embryonale dorsal-Ventral-Achse. Die Daten deuten darauf hin, dass der Verlust der faf die Aktivit&auml;t der Medea (ein homologes von Smad4) unten die Mindestanforderung f&uuml;r die angemessene Dpp-Signalisierung reduziert und dass dies wahrscheinlich wegen &uuml;berm&auml;&szlig;igen Ubiquitylation auf eine bestimmte Lysin. Diese Studie unterst&uuml;tzt die Hypothese, dass die Kontrolle der zellul&auml;ren Reaktionsf&auml;higkeit auf TGF&beta;-Signale auf der Ebene der Smad4 Ubiquitylation konservierten Mechanismus f&uuml;r die ordnungsgem&auml;&szlig;e Durchf&uuml;hrung einer Morphogen Steigung erforderlich ist.

Fett Facetten Deubiquitylation der Medea/Smad4 moduliert Interpretation der Dpp Morphogen Farbverlauf.

La capacit&agrave; di agire come morfogeni proteine secrete di &beta; (TGF&beta;) trasformando il fattore di crescita impone che la loro influenza essere strettamente regolato. Qui, segnaliamo che materna sfaccettature grassi (faf; un omologo di USP9X/FAM) &egrave; essenziale per la corretta interpretazione del zygotic gradiente morphogen Decapentaplegic (Dpp) che modelli embrionale asse dorso-ventrale. I dati suggeriscono che la perdita di faf riduce l&#39;attivit&agrave; di Medea (un omologo di Smad4) sotto il minimo necessario per un&#39;adeguata segnalazione Dpp e che questo &egrave; probabilmente a causa di eccessiva ubiquitylation su una lisina specifico. Questo studio supporta l&#39;ipotesi che il controllo della reattivit&agrave; cellulare TGF&beta; segnali a livello di ubiquitylation Smad4 &egrave; un meccanismo conservato necessario per la corretta applicazione di un gradiente di morphogen.

Deubiquitylation grasso sfaccettature di Medea/Smad4 modula interpretazione di un gradiente di morphogen Dpp.

&#x30E2;&#x30EB;&#x30D5;&#x30A9;&#x30B2;&#x30F3;&#x3068;&#x3057;&#x3066;&#x884C;&#x52D5;&#x3059;&#x308B;&#x80FD;&#x529B;&#x5206;&#x6CCC;&#x3055;&#x308C;&#x305F;&#x6210;&#x9577;&#x56E0;&#x5B50; &beta; (TGF&beta;) &#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;&#x5F7C;&#x3089;&#x306E;&#x5F71;&#x97FF;&#x3092;&#x53B3;&#x5BC6;&#x306B;&#x8ABF;&#x6574;&#x3055;&#x308C;&#x308B;&#x3053;&#x3068;&#x3092;&#x6307;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x6BCD;&#x6027;&#x8CA2;&#x732E;&#x3057;&#x305F;&#x8102;&#x80AA;&#x30D5;&#x30A1;&#x30BB;&#x30C3;&#x30C8; (faf; &#x9175;&#x7D20; usp9x &#x306F;/FAM &#x306E;&#x76F8;&#x540C;&#x7269;) &#x304C;&#x80DA;&#x80CC;&#x8179;&#x8EF8;&#x30D1;&#x30BF;&#x30FC;&#x30F3; &#x30B3;&#x30B3;&#x30E4;&#x30B7;&#x306E; Decapentaplegic &#xFF08;Dpp&#xFF09; &#x30E2;&#x30EB;&#x30D5;&#x30A9;&#x30B2;&#x30F3;&#x52FE;&#x914D;&#x306E;&#x9069;&#x5207;&#x306A;&#x89E3;&#x91C8;&#x306E;&#x305F;&#x3081;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x5831;&#x544A;&#x3057;&#x307E;&#x3059;&#x3002;&#x30C7;&#x30FC;&#x30BF;&#x3067;&#x306F;&#x3001;faf &#x306E;&#x640D;&#x5931;&#x304C; Dpp &#x5341;&#x5206;&#x306A;&#x30B7;&#x30B0;&#x30CA;&#x30EA;&#x30F3;&#x30B0;&#x306E;&#x305F;&#x3081;&#x306E;&#x5FC5;&#x8981;&#x6700;&#x4F4E;&#x9650;&#x4EE5;&#x4E0B;&#x30E1;&#x30C7;&#x30A2; (Smad4 &#x306E;&#x76F8;&#x540C;&#x7269;) &#x306E;&#x6D3B;&#x6027;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x3001;&#x3053;&#x308C;&#x304C;&#x7279;&#x5B9A;&#x306E;&#x30EA;&#x30B8;&#x30F3;&#x306B;&#x904E;&#x5270;&#x306A;&#x30E6;&#x30D3;&#x30AD;&#x30C1;&#x30F3;&#x304C;&#x3042;&#x308B;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F; TGF&beta; &#x4FE1;&#x53F7; Smad4 &#x30E6;&#x30D3;&#x30AD;&#x30C1;&#x30F3;&#x306E;&#x30EC;&#x30D9;&#x30EB;&#x3067;&#x306E;&#x7D30;&#x80DE;&#x5FDC;&#x7B54;&#x6027;&#x306E;&#x5236;&#x5FA1;&#x30E2;&#x30EB;&#x30D5;&#x30A9;&#x30B2;&#x30F3;&#x52FE;&#x914D;&#x306E;&#x9069;&#x5207;&#x306A;&#x5B9F;&#x88C5;&#x306B;&#x5FC5;&#x8981;&#x306A;&#x4FDD;&#x5B58;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x3067;&#x3042;&#x308B;&#x3068;&#x3044;&#x3046;&#x4EEE;&#x8AAC;&#x3092;&#x30B5;&#x30DD;&#x30FC;&#x30C8;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x8102;&#x80AA;&#x30D5;&#x30A1;&#x30BB;&#x30C3;&#x30C8; deubiquitylation &#x30E1;&#x30C7;&#x30A2;/Smad4 &#x306E; Dpp &#x30E2;&#x30EB;&#x30D5;&#x30A9;&#x30B2;&#x30F3;&#x52FE;&#x914D;&#x306E;&#x89E3;&#x91C8;&#x3092;&#x5909;&#x8ABF;&#x3057;&#x307E;&#x3059;&#x3002;

&#xBE44; &#xBCC0;&#xD615; &#xC131;&#xC7A5; &#xC778;&#xC790; &beta; (TGF&beta;) &#xB2E8;&#xBC31;&#xC9C8;&#xC758; &#xC5ED;&#xD560; morphogens&#xC744; &#xC218; &#xADF8;&#xB4E4;&#xC758; &#xC601;&#xD5A5;&#xB825;&#xC744; &#xC5C4;&#xACA9; &#xD558; &#xAC8C; &#xADDC;&#xC81C; &#xB420; &#xC9C0;&#xC2DC;. &#xC5EC;&#xAE30;, &#xC6B0;&#xB9AC;&#xAC00; &#xBCF4;&#xACE0; &#xC784;&#xC0B0;&#xBD80; &#xAE30;&#xACE0; &#xC9C0;&#xBC29; &#xBA74; (faf; USP9X/&#xD338; &#xCCB4;) &#xBC30;&#xC544; &#xC9C0; &#xBCF5; &#xCD95; &#xD328;&#xD134; zygotic Decapentaplegic (Dpp) morphogen &#xADF8;&#xB77C;&#xB370;&#xC774;&#xC158; &#xC801;&#xC808; &#xD55C; &#xD574;&#xC11D;&#xC744; &#xC704;&#xD574; &#xD544;&#xC218;&#xC801; &#xC774;&#xB2E4;. &#xB370;&#xC774;&#xD130; faf &#xC190;&#xC2E4; &#xC801;&#xC808; &#xD55C; Dpp &#xC2DC;&#xADF8;&#xB110;&#xB9C1;&#xC744; &#xC704;&#xD55C; &#xCD5C;&#xC18C; &#xD544;&#xC694; &#xC544;&#xB798; &#xBA54;&#xB514;&#xC544; (Smad4 &#xCCB4;)&#xC758; &#xD65C;&#xB3D9;&#xC744; &#xAC10;&#xC18C; &#xD558; &#xACE0; &#xC774;&#xAC83;&#xC774; &#xD2B9;&#xC815; lysine&#xC5D0; &#xACFC;&#xB3C4; &#xD55C; ubiquitylation &#xB54C;&#xBB38;&#xC77C; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xB294; Smad4 ubiquitylation&#xC758; &#xC218;&#xC900;&#xC5D0;&#xC11C; TGF&beta; &#xC2E0;&#xD638;&#xB97C; &#xC138;&#xD3EC; &#xBC18;&#xC751;&#xC758; &#xC81C;&#xC5B4; morphogen &#xADF8;&#xB77C;&#xB514;&#xC5B8;&#xD2B8;&#xC758; &#xC801;&#xC808; &#xD55C; &#xAD6C;&#xD604;&#xC5D0; &#xD544;&#xC694;&#xD55C; &#xBCF4;&#xC874;&#xB41C; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC740; &#xAC00;&#xC124;&#xC744; &#xC9C0;&#xC6D0; &#xD569;&#xB2C8;&#xB2E4;.

&#xBA54;&#xB514;&#xC544;/smad4&#xC758; &#xC9C0;&#xBC29; &#xBA74; deubiquitylation &#xBCC0;&#xC870; Dpp morphogen &#xADF8;&#xB77C;&#xB370;&#xC774;&#xC158;&#xC758; &#xD574;&#xC11D;.

La capacidad de las prote&iacute;nas de secreci&oacute;n Transforming Growth Factor &beta; (TGF&beta;) para actuar como morf&oacute;genos dicta que su influencia sea estrictamente regulado. Aqu&iacute;, Divulgamos que maternal contribuy&oacute; facetas grasas (faf; un hom&oacute;logo de USP9X/FAM) es esencial para la correcta interpretaci&oacute;n del cig&oacute;ticos gradiente morf&oacute;geno Decapentaplegic (Dpp) que patrones el eje dorsal-ventral embrionario. Los datos sugieren que la p&eacute;rdida de la faf reduce la actividad de Medea (un hom&oacute;logo de Smad4) por debajo de lo m&iacute;nimo necesario para una adecuada se&ntilde;alizaci&oacute;n de Dpp y que esto es probablemente debido a la excesiva ubiquitylation en una lisina espec&iacute;fica. Este estudio apoya la hip&oacute;tesis de que el control de la sensibilidad celular a TGF&beta; se&ntilde;ales a nivel de Smad4 ubiquitylation es un mecanismo conservado necesario para la correcta aplicaci&oacute;n de un gradiente de morf&oacute;geno.

Deubiquitylation grasa facetas de Medea/Smad4 modula la interpretaci&oacute;n de un gradiente de morf&oacute;geno Dpp.

CORL proteins (FUSSEL/SKOR proteins in humans) are related to Sno/Ski oncogenes but their developmental roles are unknown. We have cloned Drosophila CORL and show that its expression is restricted to distinct subsets of cells in the central nervous system. We generated a deletion of CORL and noted that homozygous individuals rarely survive to adulthood. Df(4)dCORL adult escapers display mushroom body (MB) defects and Df(4)dCORL larvae are lacking Ecdysone Receptor (EcR-B1) expression in MB neurons. This is phenocopied in CORL-RNAi and Smad2-RNAi clones in wild-type larvae. Furthermore, constitutively active Baboon (type I receptor upstream of Smad2) cannot stimulate EcR-B1 MB expression in Df(4)dCORL larvae, which demonstrates a formal requirement for CORL in Smad2 signaling. Studies of mouse Corl1 (Skor1) revealed that it binds specifically to Smad3. Overall, the data suggest that CORL facilitates Smad2 activity upstream of EcR-B1 in the MB. The conservation of neural expression and strong sequence homology of all CORL proteins suggests that this is a new family of Smad co-factors.

Drosophila CORL is required for Smad2-mediated activation of Ecdysone Receptor expression in the mushroom body.

Uncovering how a new gene acquires its function and understanding how the function of a new gene influences existing genetic networks are important topics in evolutionary biology. Here, we demonstrate nonconservation for the embryonic functions of Drosophila Bonus and its newest vertebrate relative TIF1-γ/TRIM33. We showed previously that TIF1-γ/TRIM33 functions as an ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal-ventral axis formation. Here, we show that Bonus functions as an agonist of the Decapentaplegic (Dpp) signaling network underlying dorsal-ventral axis formation in flies. The absence of conservation for the roles of Bonus and TIF1-γ/TRIM33 reveals a shift in the dorsal-ventral patterning networks of flies and mice, systems that were previously considered wholly conserved. The shift occurred when the new gene TIF1-γ/TRIM33 replaced the function of the ubiquitin ligase Nedd4L in the lineage leading to vertebrates. Evidence of this replacement is our demonstration that Nedd4 performs the function of TIF1-γ/TRIM33 in flies during dorsal-ventral axis formation. The replacement allowed vertebrate Nedd4L to acquire novel functions as a ubiquitin ligase of vertebrate-specific Smad proteins. Overall our data reveal that the architecture of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the vertebrate lineage, after separation from flies, via the incorporation of new genes.

New gene evolution in the bonus-TIF1-γ/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network.

Progenitor cells in the adult pancreas are potential sources of endocrine beta cells for treating type 1 diabetes. Previously, we identified tri-potent progenitor cells in the adult (2-4month-old) murine pancreas that were capable of self-renewal and differentiation into duct, acinar, and endocrine cells in vitro. These progenitor cells were named pancreatic colony-forming units (PCFUs). However, because PCFUs are a minor population in the pancreas (~1%) they are difficult to study. To enrich PCFUs, strategies using cell-surface marker analyses and fluorescence-activated cell sorting were developed. We found that CD133(high)CD71(low) cells, but not other cell populations, enriched PCFUs by up to 30 fold compared to the unsorted cells. CD133(high)CD71(low) cells generated primary, secondary, and subsequent colonies when serially re-plated in Matrigel-containing cultures, suggesting self-renewal abilities. In the presence of a laminin hydrogel, CD133(high)CD71(low) cells gave rise to colonies that contained duct, acinar, and Insulin(+)Glucagon(+) double-hormonal endocrine cells. Colonies from the laminin hydrogel culture were implanted into diabetic mice, and five weeks later duct, acinar, and Insulin(+)Glucagon(-) cells were detected in the grafts, demonstrating tri-lineage differentiation potential of CD133(high)CD71(low) cells. These CD133(high)CD71(low) cells will enable future studies of putative adult pancreas stem cells in vivo.

Janine C. Quijano

Diabetes and Metabolism Research Institute

Beckman Research Institute of City of Hope

In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas

Janine C. Quijano

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Diabetes and Metabolism Research Institute

Beckman Research Institute of City of Hope

In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas

Diabetes and Metabolism Research Institute