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1. Generation of recombinant hyperimmune globulins from diverse B-cell repertoires

Author

Keating, Sheila M., Mizrahi, Rena A., Adams, Matthew S., Asensio, Michael A., Benzie, Emily, Carter, Kyle P., Chiang, Yao, Edgar, Robert C., Gautam, Bishal K., Gras, Ashley, Leong, Jackson, Leong, Renee, Lim, Yoong Wearn, Manickam, Vishal A., Medina-Cucurella, Angelica V., Niedecken, Ariel R., Saini, Jasmeen, Simons, Jan Fredrik, Spindler, Matthew J., Stadtmiller, Kacy, Tinsley, Brendan, Wagner, Ellen K., Wayham, Nicholas, Tracy, LaRee, Lundberg, Carina Vingsbo, Büscher, Dirk, Terencio, Jose Vicente, Roalfe, Lucy, Pearce, Emma, Richardson, Hayley, Goldblatt, David, Ramjag, Anushka T., Carrington, Christine V. F., Simmons, Graham, Muench, Marcus O., Chamow, Steven M., Monroe, Bryan, Olson, Charles, Oguin, Thomas H., Lynch, Heather, Jeanfreau, Robert, Mosher, Rachel A., Walch, Matthew J., Bartley, Christopher R., Ross, Carl A., Meyer, Everett H., Adler, Adam S., and Johnson, David S.

Published
2021
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5. Risk of tumorigenicity in mesenchymal stromal cell–based therapies—Bridging scientific observations and regulatory viewpoints

Author

Barkholt, Lisbeth, Flory, Egbert, Jekerle, Veronika, Lucas-Samuel, Sophie, Ahnert, Peter, Bisset, Louise, Büscher, Dirk, Fibbe, Willem, Foussat, Arnaud, Kwa, Marcel, Lantz, Olivier, Mačiulaitis, Romaldas, Palomäki, Tiina, Schneider, Christian K., Sensebé, Luc, Tachdjian, Gérard, Tarte, Karin, Tosca, Lucie, and Salmikangas, Paula

Published
2013
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6. GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2

Author

Mizrahi, Rena A., primary, Lin, Wendy Y., additional, Gras, Ashley, additional, Niedecken, Ariel R., additional, Wagner, Ellen K., additional, Keating, Sheila M., additional, Ikon, Nikita, additional, Manickam, Vishal A., additional, Asensio, Michael A., additional, Leong, Jackson, additional, Medina-Cucurella, Angelica V., additional, Benzie, Emily, additional, Carter, Kyle P., additional, Chiang, Yao, additional, Edgar, Robert C., additional, Leong, Renee, additional, Lim, Yoong Wearn, additional, Simons, Jan Fredrik, additional, Spindler, Matthew J., additional, Stadtmiller, Kacy, additional, Wayham, Nicholas, additional, Büscher, Dirk, additional, Terencio, Jose Vicente, additional, Germanio, Clara Di, additional, Chamow, Steven M., additional, Olson, Charles, additional, Pino, Paula A., additional, Park, Jun-Gyu, additional, Hicks, Amberlee, additional, Ye, Chengjin, additional, Garcia-Vilanova, Andreu, additional, Martinez-Sobrido, Luis, additional, Torrelles, Jordi B., additional, Johnson, David S., additional, and Adler, Adam S., additional

Published
2022
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9. Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs

Author

Keating, Sheila M., primary, Mizrahi, Rena A., additional, Adams, Matthew S., additional, Asensio, Michael A., additional, Benzie, Emily, additional, Carter, Kyle P., additional, Chiang, Yao, additional, Edgar, Robert C., additional, Gautam, Bishal K., additional, Gras, Ashley, additional, Leong, Jackson, additional, Leong, Renee, additional, Lim, Yoong Wearn, additional, Manickam, Vishal A., additional, Medina-Cucurella, Angelica V., additional, Niedecken, Ariel R., additional, Saini, Jasmeen, additional, Simons, Jan Fredrik, additional, Spindler, Matthew J., additional, Stadtmiller, Kacy, additional, Tinsley, Brendan, additional, Wagner, Ellen K., additional, Wayham, Nicholas, additional, Tracy, LaRee, additional, Lundberg, Carina Vingsbo, additional, Büscher, Dirk, additional, Terencio, Jose Vicente, additional, Roalfe, Lucy, additional, Pearce, Emma, additional, Richardson, Hayley, additional, Goldblatt, David, additional, Ramjag, Anushka T., additional, Carrington, Christine V.F., additional, Simmons, Graham, additional, Muench, Marcus O., additional, Chamow, Steven M., additional, Monroe, Bryan, additional, Olson, Charles, additional, Oguin, Thomas H., additional, Lynch, Heather, additional, Jeanfreau, Robert, additional, Meyer, Everett H., additional, Adler, Adam S., additional, and Johnson, David S., additional

Published
2020
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17. Additional file 2: of Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis

Author

Arranz, Eduardo Martín, Arranz, María Martín, Robredo, Tomás, Mancheño-Corvo, Pablo, Menta, Ramón, Alves, Francisco, Parga, Jose Suárez De, Sanz, Pedro Mora, Rosa, Olga De La, Büscher, Dirk, Lombardo, Eleuterio, and Miguel, Fernando De

Subjects
sense organs, skin and connective tissue diseases
Abstract

Figure S2. The macroscopic damage score correlates with weight change (A) and with endoscopic score (B). (PPTX 2254 kb)

Published
2018
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18. Additional file 3: of Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis

Author

Arranz, Eduardo Martín, Arranz, María Martín, Robredo, Tomás, Mancheño-Corvo, Pablo, Menta, Ramón, Alves, Francisco, Parga, Jose Suárez De, Sanz, Pedro Mora, Rosa, Olga De La, Büscher, Dirk, Lombardo, Eleuterio, and Miguel, Fernando De

Subjects
digestive system diseases
Abstract

Figure S3. The endoscopic score correlation with the colon length 2. (PPTX 37 kb)

Published
2018
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19. Additional file 1: of Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis

Author

Arranz, Eduardo Martín, Arranz, María Martín, Robredo, Tomás, Mancheño-Corvo, Pablo, Menta, Ramón, Alves, Francisco, Parga, Jose Suárez De, Sanz, Pedro Mora, Rosa, Olga De La, Büscher, Dirk, Lombardo, Eleuterio, and Miguel, Fernando De

Subjects
sense organs, skin and connective tissue diseases
Abstract

Figure S1. Endoscopic score correlation with weight change at day 1 (A) and 11 (B). (PPTX 2289 kb)

Published
2018
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20. Biodistribution and Efficacy of Human Adipose-Derived Mesenchymal Stem Cells Following Intranodal Administration in Experimental Colitis

Author

Lopez-Santalla, Mercedes, primary, Mancheño-Corvo, Pablo, additional, Escolano, Amelia, additional, Menta, Ramon, additional, DelaRosa, Olga, additional, Abad, Jose Luis, additional, Büscher, Dirk, additional, Redondo, Juan M., additional, Bueren, Juan A., additional, Dalemans, Wilfried, additional, Lombardo, Eleuterio, additional, and Garin, Marina I., additional

Published
2017
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21. Intralymphatic Administration of Adipose Mesenchymal Stem Cells Reduces the Severity of Collagen-Induced Experimental Arthritis

Author

Mancheño-Corvo, Pablo, primary, Lopez-Santalla, Mercedes, additional, Menta, Ramon, additional, DelaRosa, Olga, additional, Mulero, Francisca, additional, del Rio, Borja, additional, Ramirez, Cristina, additional, Büscher, Dirk, additional, Bueren, Juan A., additional, Lopez-Belmonte, Juan, additional, Dalemans, Wilfried, additional, Garin, Marina I., additional, and Lombardo, Eleuterio, additional

Published
2017
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22. Cell populations having immunoregulatory activity, method for isolation and uses

Author

Büscher, Dirk, González de la Peña, Manuel Ángel, and Delgado Mora, Mario

Abstract

[EN] The present invention provides a population of connective tissue derived cells that respond to interferon-gamma (IFN-γ) by expressing indolamine-2,3-dioxygenase (IDO) for use in preventing, treating or ameliorating one or more symptoms associated with disorders in which modulation of a subject's immune system is beneficial, including, but not limited to, autoimmune diseases, inflammatory disorders, and immunologically mediated diseases including rejection of transplanted organs and tissues., [ES] Uso de una población de células aisladas de tejido adiposo caracterizado en que las células de dicha población: a) no expresan al menos un marcador específico para células presentadoras de antígeno (CPA), en donde el marcador específico para CPA es CD11b, CD11c, CD14, CD45 o HLAII, b) no expresan indolamina 2,3-dioxigenasa (IDO) de manera constitutiva, c) expresan IDO tras la estimulación con interferón-gamma (IFN-γ) y, d) presentan capacidad para diferenciarse en al menos dos linajes celulares. para la preparación o generación in vitro de células T reguladoras., Tigenix, Consejo Superior de Investigaciones Científicas (España), A1 Solicitud de patente con informe sobre el estado de la técnica

Published
2014

23. Glossar Klimawandel und Raumentwicklung

Author

Birkmann, Jörn, Böhm, Hans Reiner, Buchholz, Frank, Büscher, Dirk, Daschkeit, Achim, Ebert, Sebastian, Fleischhauer, Mark, Frommer, Birte, Köhler, Stefan, Kufeld, Walter, Lenz, Susanne, Overbeck, Gerhard, Schanze, Jochen, Schlipf, Sonja, Sommerfeldt, Petra, Stock, Manfred, Vollmer, Maike, Walkenhorst, Oliver, and Akademie für Raumforschung und Landesplanung - Leibniz-Forum für Raumwissenschaften

Subjects
Landscaping and area planning, Städtebau, Raumplanung, Landschaftsgestaltung, Klimawandel, Ecology, Area Development Planning, Regional Research, Raumplanung und Regionalforschung, Ecology, Environment, Ökologie und Umwelt, climate change, Raumplanung, Ökologie, ddc:577, spatial planning, ddc:710
Abstract

Das vorliegende Glossar "Klimawandel und Raumentwicklung" ist ein Ergebnis des Arbeitskreises "Klimawandel und Raumplanung" der ARL, der sich seit Anfang 2007 mit den Herausforderungen und Aufgaben, die sich durch den Klimawandel für die Raumentwicklung und Raumplanung stellen, befasst. Terminologien sind für ein gemeinsames Verständnis und eine gute Kommunikation unabdingbar. Nicht immer meinen unterschiedliche Personen – oder auch Disziplinen – mit demselben Wort auch denselben Sachverhalt. Dabei gibt es nicht immer unbedingt die eine "richtige" Definition, sondern im Gegenteil unterschiedliche Sichtweisen, die alle ihre Berechtigung haben – deren Verständnis jedoch auch für diejenigen wichtig ist, die einen anderen Blickwinkel einnehmen. Dieses Glossar umfasst zentrale Begriffe, die in der Diskussion um den Klimawandel aus Sicht der Raumwissenschaften von Bedeutung sind: von "Anpassung" und "Bewältigungskapazität" über "Climate Proofing" und "Szenarien" bis hin zu "Vulnerabilität". Das Glossar bietet nicht nur Definitionen, sondern stellt unterschiedliche Perspektiven und Begriffsverständnisse, die z.B. in einzelnen Disziplinen gebräuchlich sind, vor. Somit handelt es sich im Grunde um ein "erweitertes" Glossar, das über die reine Begriffserklärung hinausgeht. Zusätzlich sind die gebräuchlichen englischen Begriffe angegeben, sofern sie auch im deutschsprachigen Raum verwendet werden.

Published
2011

24. Células madre del estroma derivadas de tejido adiposo para su uso en el tratamiento de SRIS

Author

Delgado, Mario, Büscher, Dirk, Gonzalez-Rey, Elena, Universidad de Sevilla. Psicología Social, and Consejo Superior de Investigaciones Científicas (CSIC)|Universidad de Sevilla|TiGenix

Abstract

Una composición que comprende células madre del estroma derivadas de tejido adiposo (CEA), para su uso en el tratamiento de síndrome de respuesta inflamatoria sistémica (SRIS) en un sujeto.

Published
2011

25. Uses of mesenchymal stem cells

Author

Delgado, M., González-Rey, Elena, and Büscher, Dirk

Subjects
SIRS, Mesenchymal stem cells, humanities
Abstract

The invention relates to the use of mesenchymal stem cells (MSCs) for treating systemic infiammatory response syndrome (SIRS) in a subject. The invention provides compositions, uses and methods for the treatment of SIRS., Cellerix SA, Consejo Superior de Investigaciones Científicas (España), A2 Solicitud de patentes sin informe sobre el estado de la técnica

Published
2008

26. Poblaciones de células que tienen actividad inmunorreguladora, método de aislamiento y usos

Author

Büscher, Dirk, González de la Peña, Manuel Ángel, Delgado Mora, Mario, and WO2007039150 A3 (2007-08-23)

Abstract

Una composición farmacéutica que comprende una población de células aisladas de tejido conjuntivo y un vehículo farmacéuticamente aceptable caracterizada en que las células de dicha población: de células expresan indolamina 2,3-dioxigenasa (IDO) tras la estimulación con interferón gamma (IFN-γ), para uso en el tratamiento de una enfermedad inflamatoria en un sujeto, en la que la enfermedad inflamatoria es enfermedad inflamatoria del intestino, en la que las células de la población celular se prepararan mediante un método que comprende cultivar células sin diferenciación sobre una superficie sólida en presencia de un medio de cultivo adecuado o un suero adecuado e incubar las células en condiciones que permitan a las células adherirse a la superficie sólida y proliferar, y en la que el método comprende seleccionar células que quedan adheridas a la superficie sólida después de al menos dos pases.1, TIGENIX, Consejo Superior de Investigaciones Científicas (España), T3 Traducción de patente europea

Published
2005

27. Células madre del estroma derivadas de tejido adiposo para su uso en el tratamiento de SRIS

Author

Universidad de Sevilla. Psicología Social, Delgado, Mario, Büscher, Dirk, Gonzalez-Rey, Elena, Universidad de Sevilla. Psicología Social, Delgado, Mario, Büscher, Dirk, and Gonzalez-Rey, Elena

Abstract

Una composición que comprende células madre del estroma derivadas de tejido adiposo (CEA), para su uso en el tratamiento de síndrome de respuesta inflamatoria sistémica (SRIS) en un sujeto.

Published
2011

28. Uses of mesenchymal stem cells

Author

Delgado, M., González-Rey, Elena, Büscher, Dirk, Delgado, M., González-Rey, Elena, and Büscher, Dirk

Abstract

The invention relates to the use of mesenchymal stem cells (MSCs) for treating systemic infiammatory response syndrome (SIRS) in a subject. The invention provides compositions, uses and methods for the treatment of SIRS.

Published
2010

29. Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses

Author

González, Manuel Ángel, González-Rey, Elena, Rico, L., Büscher, Dirk, Delgado, M., González, Manuel Ángel, González-Rey, Elena, Rico, L., Büscher, Dirk, and Delgado, M.

Abstract

Background & Aims: Crohn's disease is a chronic disease characterized by severe T-helper (Th)1 cell-driven inflammation of the colon partially caused by a loss of immune tolerance against mucosal antigens. Mesenchymal stem cells were recently described to suppress effector T-cell responses and have therapeutic effects in some immune disorders. Here, we investigated the potential therapeutic effects of human adipose-derived mesenchymal stem cells (hASCs) in a model of inflammatory bowel disease. Methods: Mice with trinitrobenzene sulfonic acid-induced colitis were treated with hASCs after onset of disease and clinical scores were evaluated. Inflammatory response was determined by measuring the levels of different inflammatory mediators in colon and serum. Th1-mediated effector responses were evaluated by determining the proliferation and cytokine profile of activated mesenteric lymph node cells. The number of regulatory T cells and the suppressive capacity on Th1 cell responses was determined. Results: Systemic infusion of hASCs or murine ASCs ameliorated the clinical and histopathologic severity of colitis, abrogating body weight loss, diarrhea, and inflammation and increasing survival (P < .001). This therapeutic effect was mediated by down-regulating both Th1-driven autoimmune and inflammatory responses. ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin-10 levels (P < .001), directly acting on activated macrophages. hASCs also impaired Th1 cell expansion and induced/activated CD4+CD25+FoxP3+ regulatory T cells with suppressive capacity on Th1 effector responses in vitro and in vivo (P < .001). Conclusions: hASCs emerge as key regulators of immune tolerance and as attractive candidates for a cell-based therapy for Crohn's disease. © 2009 AGA Institute.

Published
2009

31. Requirement of IFN-γ–Mediated Indoleamine 2,3-Dioxygenase Expression in the Modulation of Lymphocyte Proliferation by Human Adipose–Derived Stem Cells

Author

DelaRosa, Olga, primary, Lombardo, Eleuterio, additional, Beraza, Aitor, additional, Mancheño-Corvo, Pablo, additional, Ramirez, Cristina, additional, Menta, Ramón, additional, Rico, Laura, additional, Camarillo, Eva, additional, García, Laura, additional, Abad, José Luis, additional, Trigueros, Cesar, additional, Delgado, Mario, additional, and Büscher, Dirk, additional

Published
2009
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35. MKP3 mediates the cellular response to FGF8 signalling in the vertebrate limb

Author

Kawakami, Yasuhiko, primary, Rodríguez-León, Joaquín, additional, Koth, Christopher M., additional, Büscher, Dirk, additional, Itoh, Tohru, additional, Raya, Ángel, additional, Ng, Jennifer K., additional, Esteban, Concepción Rodríguez, additional, Takahashi, Shigeru, additional, Henrique, Domingos, additional, Schwarz, May-Fun, additional, Asahara, Hiroshi, additional, and Izpisúa Belmonte, Juan Carlos, additional

Published
2003
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36. Notch activity inducesNodalexpression and mediates the establishment of left–right asymmetry in vertebrate embryos

Author

Raya, Ángel, primary, Kawakami, Yasuhiko, additional, Rodrı́guez-Esteban, Concepción, additional, Büscher, Dirk, additional, Koth, Christopher M., additional, Itoh, Tohru, additional, Morita, Masanobu, additional, Raya, R. Marina, additional, Dubova, Ilir, additional, Bessa, Joaquı́n Grego, additional, de la Pompa, José Luis, additional, and Belmonte, Juan Carlos Izpisúa, additional

Published
2003
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37. Obtención de células madre inmortalizadas derivadas de lipoaspirado para su diferenciación hacia diferentes linajes.

Author

Magjarevic, R., Nagel, J. H., Müller-Karger, Carmen, Wong, Sara, La Cruz, Alexandra, Londoño, Carolina, Büscher, Dirk, Beraza, Aitor, Abad, José Luis, and Camarillo, Eva

Abstract

Adult stem cells are considered the present and the future in gene therapy. One of the sources for adult stem cells is adipose tissue where CMDL (lipoaspiration derived stem cells) are obtained, CMDL are well known for their autorenovation capacity, long term viability and potential to differentiate to diverse cellular types in vitro, like adipogenic, condrogenic, miogenic, osteogenic eventhough neurons. [ABSTRACT FROM AUTHOR]

Published
2008
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38. The limb identity geneTbx5promotes limb initiation by interacting withWnt2bandFgf10

Author

Ng, Jennifer K., primary, Kawakami, Yasuhiko, additional, Büscher, Dirk, additional, Raya, Ángel, additional, Itoh, Tohru, additional, Koth, Christopher M., additional, Esteban, Concepción Rodríguez, additional, Rodríguez-León, Joaquín, additional, Garrity, Deborah M., additional, Fishman, Mark C., additional, and Belmonte, Juan Carlos Izpisúa, additional

Published
2002
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45. The limb identity gene Tbx5 promotes limb initiation by interacting with Wnt2b and Fgf10

Author

Ng, Jennifer K., Kawakami, Yasuhiko, Büscher, Dirk, Raya, Ángel, Itoh, Tohru, Koth, Christopher M., Esteban, Concepción Rodríguez, Rodríguez-León, Joaquín, Garrity, Deborah M., Fishman, Mark C., and Belmonte, Juan Carlos Izpisúa

Abstract

A major gap in our knowledge of development is how the growth and identity of tissues and organs are linked during embryogenesis. The vertebrate limb is one of the best models to study these processes. Combining mutant analyses with gain- and loss-of-function approaches in zebrafish and chick embryos, we show that Tbx5, in addition to its role governing forelimb identity,is both necessary and sufficient for limb outgrowth. We find thatTbx5 functions downstream of WNT signaling to regulateFgf10, which, in turn, maintains Tbx5 expression during limb outgrowth. Furthermore, our results indicate that Tbx5 andWnt2b function together to initiate and specify forelimb outgrowth and identity. The molecular interactions governed by members of the T-box,Wnt and Fgf gene families uncovered in this study provide a framework for understanding not only limb development, but how outgrowth and identity of other tissues and organs of the embryo may be regulated.

Published
2002
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46. The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

Author

Takahashi, Motohisa, Tamura, Koji, Büscher, Dirk, Masuya, Hiroshi, Yonei-Tamura, Sayuri, Matsumoto, Ken, Naitoh-Matsuo, Mayumi, Takeuchi, Jun, Ogura, Keiko, Shiroishi, Toshihiko, Ogura, Toshihiko, and Izpisúa Belmonte, Juan Carlos

Abstract

We have determined that Strong’s Luxoid (lstJ) mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.

Published
1998
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47. Expression profile of <TOGGLE>Gli</TOGGLE> family members and <TOGGLE>Shh</TOGGLE> in normal and mutant mouse limb development

Author

Büscher, Dirk and Rüther, Ulrich

Abstract

Gli genes represent a small family, encoding zinc-finger proteins of the Krüppel-type. The family consists of Gli(1), Gli2, and Gli3, all of which are expressed in the developing mouse limb bud. To assess the role of the Gli family and Sonic hedgehog (Shh) in mouse limb development, we compared the expression domains of all three Gli genes and of Shh. Although each Gli gene has its own distinct expression pattern in limb buds, at 10.5–11.5 dpc all three genes were found not to be expressed in the posterior region, the presumptive Shh expression domain. This transient mutually exclusive expression suggested a potential interaction between Gli genes and Shh. To address this matter, we analysed the expression of Gli genes and Shh in two polydactyly mouse mutants, Extra toes (Xt) and Hemimelic-extra toes (Hx) which express Shh ectopically in the anterior region of the limb field. Since Xt mice lack Gli3 expression, the ectopic Shh expression is genetically linked to the absence of Gli3. In Hx mice we found a down-regulation of Gli3 in the anterior region of the limb bud. In both mutants Gli2 expression pattern was not altered, whereas Gli1 expression was anteriorly up-regulated adjacent to the ectopic Shh domain. These results strongly suggest a positive regulation of Gli1 by Shh and a negative interaction between Shh and Gli3. Dev. Dyn. 1998;211:88–96.© 1998 Wiley-Liss, Inc.

Published
1998
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50. Tbx3 controls the fate of hepatic progenitor cells in liver development by suppressing p19ARF expression.

Author

Suzuki, Atsushi, Sekiya, Sayaka, Büscher, Dirk, Belmonte, Juan Carlos Izpisúa, and Taniguchi, Hideki

Subjects
LIVER, CELL differentiation, MORPHOGENESIS, TUMORS, LABORATORY mice
Abstract

Although the T-box family of transcription factors function in many different tissues, their role in liver development is unknown. Here we show that Tbx3, the T-box gene that is mutated in human ulnar-mammary syndrome, is specifically expressed in multipotent hepatic progenitor cells, 'hepatoblasts', isolated from the developing mouse liver. Tbx3-deficient hepatoblasts presented severe defects in proliferation as well as uncontrollable hepatobiliary lineage segregation, including the promotion of cholangiocyte (biliary epithelial cell) differentiation, which thereby caused abnormal liver development. Deletion of Tbx3 resulted in the increased expression of the tumor suppressor p19ARF (Cdkn2a), which in turn induced a growth arrest in hepatoblasts and activated a program of cholangiocyte differentiation. Thus, Tbx3 plays a crucial role in controlling hepatoblast proliferation and cell-fate determination by suppressing p19ARF expression and thereby promoting liver organogenesis. [ABSTRACT FROM AUTHOR]

Published
2008

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