Área de Concentração: 10132
Concentration area: 10132
Criação: 13/09/2022
Creation: 13/09/2022
Ativação: 13/09/2022
Activation: 13/09/2022
Nr. de Créditos: 2
Credits: 2
Carga Horária:
Workload:
Teórica (por semana) |
Theory (weekly) |
Prática (por semana) |
Practice (weekly) |
Estudos (por semana) |
Study (weekly) |
Duração | Duration | Total | Total |
---|---|---|---|---|---|---|---|---|---|
15 | 10 | 5 | 1 semanas | 1 weeks | 30 horas | 30 hours |
Docentes Responsáveis:
Professors:
Maria Angélica Miglino
Fabiana Fernandes Bressan
Lawrence Charles Smith
Objetivos:
Esta disciplina tem como objetivo introduzir o histórico da origem e o conceito das células tronco pluripotentes induzidas (iPSC), de forma que os alunos possam compreender os mecanismos pelos quais são realizados a reprogramação celular, bem como suas prováveis aplicações terapêuticas na medicina veterinária. Para o uso efetivo e para a realização da diferenciação destas células é necessário a realização de alguns métodos para a validação experimental da pluripotência das iPSCs.
Objectives:
This discipline aims to introduce the history, origins and concept of induced pluripotent stem cells (iPSCs), so that students can understand the mechanisms by which cell reprogramming is performed, as well as their probable therapeutic applications in veterinary medicine. For the effective use and differentiation of these cells, it is necessary to perform some methods for the experimental validation of the pluripotency of iPSCs.
Justificativa:
Em 2006, descobriu-se que as células somáticas podem ser reprogramadas a um estado de pluripotência semelhante às células-tronco embrionárias (TAKAHASHI; YAMANAKA, 2006), através da expressão de fatores de transcrição, tais como Oct4, Sox2, Klf4, cMyc, Nanog, Lin28, Nr5a2 e Rarg (TAKAHASHI; YAMANAKA, 2006; TAKAHASHI et al., 2007a; TAKAHASHI et al., 2007b; YU et al., 2009; BAYART; COHEN-HAGUENAUER, 2013; ZHOU; ZENG, 2013). Os produtos deste processo de reprogramação são referidos como células tronco pluripotentes induzidas (iPSC). As iPSCs possuem capacidade de auto renovação, bem como podem se diferenciar em vários tipos de células adultas, mostrando grande potencial do seu uso na área da medicina regenerativa (SINGH et al., 2015).
Rationale:
In 2006, it was found that somatic cells can be reprogrammed to a state of pluripotency similar to embryonic stem cells (TAKAHASHI; YAMANAKA, 2006), through the expression of transcription factors such as Oct4, Sox2, Klf4, cMyc, Nanog, Lin28, Nr5a2 and Rarg (TAKAHASHI; YAMANAKA, 2006; TAKAHASHI et al., 2007a; TAKAHASHI et al., 2007b; YU et al., 2009; BAYART, BAYART, 2010. COHEN-HAGUENAUER, 2013; Zhou; ZENG, 2013). The products of this reprogramming process are referred to as induced pluripotent stem cells (iPSCs). iPSCs have self-renewal capacity, as well as can differentiate in various types of adult cells, showing great potential for their use in the area of regenerative medicine (SINGH et al., 2015).
Conteúdo:
1. Origem histórica; 2. Mecanismos biológicos da reprogramação celular; 3. Validação experimental da pluripotência; 4. Obtenção de iPSC em espécies domésticas; 5. Aplicações terapêuticas na medicina veterinária.
Content:
1. Historical origin; 2. Biological mechanisms of cellular reprogramming; 3. Experimental validation of pluripotency; 4. Obtaining iPSC in domestic species; 5. Therapeutic applications in veterinary medicine.
Forma de Avaliação:
A avaliação será baseada na presença dos alunos (mínimo 75%); assim como a participação na leitura e discussão de artigos científicos referentes ao tema (25%), cuja nota final (0-10), obtida pela média aritmética simples, determinará o conceito final (A,B,C,R), considerando os respectivos intervalos: 10-9 (A); 8-7 (B); 6-5 (C); 4-0 (R).
Type of Assessment:
The evaluation will be based on the presence of students (minimum 75%); as well as participation in the reading and discussion of scientific articles on the subject (25%), whose final score (0-10), obtained by the simple arithmetic mean, will determine the final concept (A,B,C,R), considering the respective intervals: 10-9 (A); 8-7 (B); 6-5 (C); 4-0 (R).
Bibliografia:
1. BAYART, E.;COHEN-HAGUENAUER, O. Technological overview of iPS induction from human adult somatic cells. Current Gene Therapy, v. 13, n. 2, p. 73–92, 2013. 2. SINGH, V.K.; KUMAR, N.; KALSAN, M.; SAINI, A.; CHANDRA, R. Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs). J Stem Cells, v. 10, n. 1, p. 43-62, 2015. 3. TAKAHASHI, K.; YAMANAKA, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, v. 126, n. 4, p. 663-676, 2006. 4. TAKAHASHI, K.; OKITA, K.; NAKAGAWA, M.; YAMANAKA, S. Induction of pluripotent stem cells from fibroblast cultures. Nature Protocols, v. 2, n. 12, p. 3081-3089, 2007a. 5. TAKAHASHI, K.; TANABE, K.; OHNUKI, M.; NARITA, M.; ICHISAKA, T.; YAMANAKA, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, v. 131, n. 5, p. 861-872, 2007b. 6. YU, J., HU, K., SMUGA-OTTO, K., TIAN, S., STEWART, R., SLUKVIN, I., THOMSON, J. A. Human induced pluripotent stem cells free of vector and transgene sequences. Science, v. 324, n. 5928, p. 797–801, 2009. 7. ZHOU, Y. Y.; ZENG, F. Integration-free methods for generating induced pluripotent stem cells. Genomics Proteomics Bioinformatics, v. 11, n. 5, p. 284–287, 2013. 8. Dutton, L. C., Dudhia, J., Guest, D. J., & Connolly, D. J. (2019). Inducing pluripotency in the domestic cat (Felis catus). Stem Cells and Development, 28(19), 1299-1309. 9. Machado, L. S., Pieri, N. C. G., Botigelli, R. C., Castro, R. V. G., de Souza, A. F., de Lima, M. A., ... & Bressan, F. F. (2020). 217 Induction and differentiation of porcine induced pluripotent stem cells into neuronal precursor cell-like cells. Reproduction, Fertility and Development, 32(2), 236-237. 10. Menon, D. V., Bhaskar, S., Sheshadri, P., Joshi, C. G., Patel, D., & Kumar, A. (2021). Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of naïve or primed state in comparison to mouse and human iPSCs. Life Sciences, 264, 118701. 11. Amilon, K. R., Cortes-Araya, Y., Moore, B., Lee, S., Lillico, S., Breton, A., ... & Donadeu, F. X. (2018). Generation of functional myocytes from equine induced pluripotent stem cells. Cellular Reprogramming (Formerly" Cloning and Stem Cells"), 20(5), 275-281. 12. Tukker, A. M., Wijnolts, F. M., Groot, A. D., Wubbolts, R. W., & Westerink, R. H. (2019). In vitro techniques for assessing neurotoxicity using human iPSC-derived neuronal models. In Cell Culture Techniques (pp. 17-35). Humana, New York, NY. 13. Mu, A., Hira, A., Niwa, A., Osawa, M., Yoshida, K., Mori, M., ... & Takata, M. (2021). Analysis of disease model iPSCs derived from patients with a novel Fanconi anemia–like IBMFS ADH5/ALDH2 deficiency. Blood, 137(15). 14. Maeda, T., Nagano, S., Kashima, S., Terada, K., Agata, Y., Ichise, H., ... & Kawamoto, H. (2020). Regeneration of tumor-antigen-specific cytotoxic T lymphocytes from iPSCs transduced with exogenous TCR genes. Molecular Therapy-Methods & Clinical Development, 19, 250-260. 15. Alysandratos, K. D., Russo, S. J., Petcherski, A., Taddeo, E. P., Acín-Pérez, R., Villacorta-Martin, C., ... & Kotton, D. N. (2021). Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease. Cell reports, 36(9), 109636. 16. Araki, R., Hoki, Y., Suga, T., Obara, C., Sunayama, M., Imadome, K., ... & Abe, M. (2020). Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency. Nature communications, 11(1), 1-17. 17. Brooks, I. R., Garrone, C. M., Kerins, C., Kiar, C. S., Syntaka, S., Xu, J. Z., ... & Watt, F. M. (2022). Functional genomics and the future of iPSCs in disease modeling. Stem cell reports. 18. Iberite, F., Gruppioni, E., & Ricotti, L. (2022). Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges. NPJ Regenerative Medicine, 7(1), 1-30. 19. Chen, C., & Guan, M. X. (2022). Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients. Human Molecular Genetics. 20. Kim, B. W., Ryu, J., Jeong, Y. E., Kim, J., & Martin, L. J. (2020). Human motor neurons with SOD1-G93A mutation generated from CRISPR/Cas9 gene-Edited iPSCs develop pathological features of amyotrophic lateral sclerosis. Frontiers in cellular neuroscience, 14, 604171.
Bibliography:
1. BAYART, E.;COHEN-HAGUENAUER, O. Technological overview of iPS induction from human adult somatic cells. Current Gene Therapy, v. 13, n. 2, p. 73–92, 2013. 2. SINGH, V.K.; KUMAR, N.; KALSAN, M.; SAINI, A.; CHANDRA, R. Mechanism of Induction: Induced Pluripotent Stem Cells (iPSCs). J Stem Cells, v. 10, n. 1, p. 43-62, 2015. 3. TAKAHASHI, K.; YAMANAKA, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, v. 126, n. 4, p. 663-676, 2006. 4. TAKAHASHI, K.; OKITA, K.; NAKAGAWA, M.; YAMANAKA, S. Induction of pluripotent stem cells from fibroblast cultures. Nature Protocols, v. 2, n. 12, p. 3081-3089, 2007a. 5. TAKAHASHI, K.; TANABE, K.; OHNUKI, M.; NARITA, M.; ICHISAKA, T.; YAMANAKA, S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, v. 131, n. 5, p. 861-872, 2007b. 6. YU, J., HU, K., SMUGA-OTTO, K., TIAN, S., STEWART, R., SLUKVIN, I., THOMSON, J. A. Human induced pluripotent stem cells free of vector and transgene sequences. Science, v. 324, n. 5928, p. 797–801, 2009. 7. ZHOU, Y. Y.; ZENG, F. Integration-free methods for generating induced pluripotent stem cells. Genomics Proteomics Bioinformatics, v. 11, n. 5, p. 284–287, 2013. 8. Dutton, L. C., Dudhia, J., Guest, D. J., & Connolly, D. J. (2019). Inducing pluripotency in the domestic cat (Felis catus). Stem Cells and Development, 28(19), 1299-1309. 9. Machado, L. S., Pieri, N. C. G., Botigelli, R. C., Castro, R. V. G., de Souza, A. F., de Lima, M. A., ... & Bressan, F. F. (2020). 217 Induction and differentiation of porcine induced pluripotent stem cells into neuronal precursor cell-like cells. Reproduction, Fertility and Development, 32(2), 236-237. 10. Menon, D. V., Bhaskar, S., Sheshadri, P., Joshi, C. G., Patel, D., & Kumar, A. (2021). Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of naïve or primed state in comparison to mouse and human iPSCs. Life Sciences, 264, 118701. 11. Amilon, K. R., Cortes-Araya, Y., Moore, B., Lee, S., Lillico, S., Breton, A., ... & Donadeu, F. X. (2018). Generation of functional myocytes from equine induced pluripotent stem cells. Cellular Reprogramming (Formerly" Cloning and Stem Cells"), 20(5), 275-281. 12. Tukker, A. M., Wijnolts, F. M., Groot, A. D., Wubbolts, R. W., & Westerink, R. H. (2019). In vitro techniques for assessing neurotoxicity using human iPSC-derived neuronal models. In Cell Culture Techniques (pp. 17-35). Humana, New York, NY. 13. Mu, A., Hira, A., Niwa, A., Osawa, M., Yoshida, K., Mori, M., ... & Takata, M. (2021). Analysis of disease model iPSCs derived from patients with a novel Fanconi anemia–like IBMFS ADH5/ALDH2 deficiency. Blood, 137(15). 14. Maeda, T., Nagano, S., Kashima, S., Terada, K., Agata, Y., Ichise, H., ... & Kawamoto, H. (2020). Regeneration of tumor-antigen-specific cytotoxic T lymphocytes from iPSCs transduced with exogenous TCR genes. Molecular Therapy-Methods & Clinical Development, 19, 250-260. 15. Alysandratos, K. D., Russo, S. J., Petcherski, A., Taddeo, E. P., Acín-Pérez, R., Villacorta-Martin, C., ... & Kotton, D. N. (2021). Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease. Cell reports, 36(9), 109636. 16. Araki, R., Hoki, Y., Suga, T., Obara, C., Sunayama, M., Imadome, K., ... & Abe, M. (2020). Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency. Nature communications, 11(1), 1-17. 17. Brooks, I. R., Garrone, C. M., Kerins, C., Kiar, C. S., Syntaka, S., Xu, J. Z., ... & Watt, F. M. (2022). Functional genomics and the future of iPSCs in disease modeling. Stem cell reports. 18. Iberite, F., Gruppioni, E., & Ricotti, L. (2022). Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges. NPJ Regenerative Medicine, 7(1), 1-30. 19. Chen, C., & Guan, M. X. (2022). Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients. Human Molecular Genetics. 20. Kim, B. W., Ryu, J., Jeong, Y. E., Kim, J., & Martin, L. J. (2020). Human motor neurons with SOD1-G93A mutation generated from CRISPR/Cas9 gene-Edited iPSCs develop pathological features of amyotrophic lateral sclerosis. Frontiers in cellular neuroscience, 14, 604171.
Tipo de oferecimento da disciplina:
Presencial
Class type:
Presencial