Investigation of cellular and molecular mechanisms on in vitro induced toti- and pluripotency acquisition - a translational approach

• Grant number: 15/26818-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: October 01, 2016
• End date: January 31, 2023
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Fabiana Fernandes Bressan
• Grantee: Fabiana Fernandes Bressan
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated researchers: André Furugen Cesar de Andrade ; Carlos Eduardo Ambrósio ; Daniele dos Santos Martins ; Dimas Tadeu Covas ; Felipe Perecin ; Flávio Vieira Meirelles ; José Eduardo Krieger ; Lawrence Charles Smith ; Simone Kashima Haddad ; Virginia Picanço e Castro ; Wilson Araújo da Silva Junior
• Associated scholarship(s): 22/07318-5 - Generation of induced pluripotent stem cells (iPSCs) from adult camelid cells followed by differentiation into a muscle cell line, BP.IC; 20/15122-8 - Induced pluripotent cells as an alternative for viable gametes production, BP.DR; 21/12604-4 - Culture and characterization of the reprogrammed cells in vitro: generation and maintenance of the pluripotency in different species, BP.TT; + associated scholarships 21/08095-7 - In vitro gamete derivation and production from porcine induced pluripotent stem cells (piPSCs), BP.PD; 20/07921-8 - Generation of induced pluripotency stem cells (iPSCs) from adult camelid cells, BP.IC; 20/10503-3 - Profile of germinative, epigenetic and pluripotency markers in male and female germ cells during embryonic and adult development in swine, BP.IC; 20/15897-0 - Characterization of induced pluripotent stem cells (iPSCs) from dogs (Canis lupus familiaris) healthy or diagnosed with Cognitive Dysfunction Syndrome, BP.IC; 21/04232-0 - Culture and characterization of the reprogrammed cells in vitro - generation and maintenance of the pluripotency in different species., BP.TT; 19/20527-0 - Generation of primordial germ cells from induced pluripotent stem cells through a non-integrative system: a model based on non-human primates, BP.PD; 20/08562-1 - Generation of induced pluripotency stem cells (iPSCs) from adult cells of small red deer (Mazama bororo), BP.IC; 20/10270-9 - In vitro culture of reprogrammed cells: pluripotency generation and maintenance, BP.TT; 20/03963-8 - Interfaces of the generation of induced pluripotent stem cells (iPSC) from jaguar (Panthera onca) in favor of genetic and population conservation, BP.IC; 20/03487-1 - Influence of the gaseous atmosphere on the expression of genes regulating epigenetic changes during in vitro cell reprogramming (cell generation iPSCs), BP.IC; 19/25134-6 - In vitro culture of reprogrammed cells - pluripotency generation and maintenance., BP.TT; 19/02811-2 - In vitro cellular reprogramming to pluripotency (iPS) in the swine model from non-transgenic and non-invasive methodology, BP.MS; 19/03242-1 - Equine induced pluripotent stem cell (eiPSC) generation from episomal mechanism, BP.IC; 18/24520-7 - Epigenetic modification mechanisms are activated by reactive oxygen (ro) in bovine induced pluripotent stem cells, BP.IC; 18/04009-6 - Effects of low oxygen tension in the reprogramming efficiency and manutention of induced pluripotent stem cells in equine, BP.DR; 16/16841-2 - Trophectoderm complementation assay for IPS cells: a proposal for assessing pluripotency in cattle, BP.DR; 17/02049-8 - Generation and cell culture of pluripotent cells in the pig model: the search for generation and differential characterization between primed and naïve cells, BP.IC; 17/02159-8 - Induction of cell pluripotency and in vitro differentiation in the porcine model as a translational model, BP.MS; 16/19580-5 - Investigation of cellular and molecular mechanisms on in vitro induced toti- and pluripotency acquisition - a translational approach., BP.JP - associated scholarships

Abstract

Cellular reprogramming technologies are a promising tool for the understanding of pluripotent cell biology and also to study several genetic and tissue-related disorders, enabling the investigation of the molecular events responsible for the acquisition of competency into pluri- and totipotency. This proposal aims to consolidate procedures for the generation of induced pluripotent stem (iPS) cells and germ cells in vitro from domestic species of commercial and biomedical interest (focus on cattle and swine) by investigating cellular and molecular mechanisms involved in cellular reprogramming, and by disseminating protocols and biological material for collaborations. Three general goals are proposed: 1) The standardization of safe and reproducible protocols of iPS generation, 2) The generation of germ cells, gametes and embryos from in vitro cultured cells, and 3) The investigation of transcriptional and epigenetic mechanisms of cellular reprogramming in domestic animals. The results achieved by this proposal will consolidate national research on nuclear and epigenetic reprogramming, allow the international insertion through scientific collaborations and high impact scientific publications, finally resulting in the formation of a multidisciplinary, competitive and collaborative research group both nationally and internationally. (AU)

Scientific publications

(22)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARACHO TRINDADE HILL, AMANDA; SPERI ALVES, ANTONIO ALEXANDRE; DA SILVA NUNES BARRETO, RODRIGO; FERNANDES BRESSAN, FABIANA; MIGLINO, MARIA ANGELICA; MANSANO GARCIA, JOAQUIM. Placental scaffolds have the ability to support adipose-derived cells differentiation into osteogenic and chondrogenic lineages. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, v. 14, n. 11, SEP 2020. (15/14535-9, 15/26818-5)

RECCHIA, KAIANA; MACHADO, LUCAS SIMOES; BOTIGELLI, RAMON CESAR; PIERI, NAIRA CAROLINE GODOY; BARBOSA, GABRIELA; DE CASTRO, RAQUEL VASCONCELOS GUIMARAES; MARQUES, MARIANA GROKE; PESSOA, LAIS VICARI DE FIGUEIREDO; FANTINATO NETO, PAULO; MEIRELLES, FLAVIO VIEIRA; et al. In vitro induced pluripotency from urine-derived cells in porcine. WORLD JOURNAL OF STEM CELLS, v. 14, n. 3, p. 14-pg., 2022-03-26. (15/26818-5, 13/08135-2, 19/02811-2)

DE CASTRO, RAQUEL V. G.; PIERI, NAIRA C. G.; FANTINATO NETO, PAULO; GRIZENDI, BIANCA M.; DORIA, RENATA G. S.; MEIRELLES, FLAVIO V.; SMITH, LAWRENCE C.; GARCIA, JOAQUIM M.; BRESSAN, FABIANA F.. In Vitro Induction of Pluripotency from Equine Fibroblasts in 20% or 5% Oxygen. STEM CELLS INTERNATIONAL, v. 2020, NOV 26 2020. (13/08135-2, 18/04009-6, 15/26818-5)

RECCHIA, KAIANA; PESSOA, LAIS VICARI DE FIGUEIREDO; PIERI, NAIRA CAROLINE GODOY; PIRES, PEDRO RATTO LISBOA; BRESSAN, FABIANA FERNANDES. Influence of Cell Type in In Vitro Induced Reprogramming in Cattle. LIFE-BASEL, v. 12, n. 8, p. 10-pg., 2022-08-01. (19/02811-2, 13/08135-2, 15/26818-5)

BOTIGELLI, RAMON CESAR; PIERI, NAIRA CAROLINA GODOY; BESSI, BRENDON WILLIAM; MACHADO, LUCAS SIMOES; BRIDI, ALESSANDRA; DE SOUZA, ALINE FERNANDA; RECCHIA, KAIANA; NETO, PAULO FANTINATO; ROSS, PABLO JUAN; BRESSAN, FABIANA FERNANDES; et al. Acquisition and maintenance of pluripotency are influenced by fibroblast growth factor, leukemia inhibitory factor, and 2i in bovine-induced pluripotent stem cells. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 10, p. 12-pg., 2022-09-14. (19/10751-0, 13/08135-2, 16/16841-2, 15/26818-5, 12/50533-2)

DE FIGUEIREDO PESSOA, LAIS VICARI; LISBOA PIRES, PEDRO RATTO; DEL COLLADO, MAITE; GODOY PIERI, NAIRA CAROLINE; RECCHIA, KAIANA; SOUZA, ALINE FERNANDA; PERECIN, FELIPE; DA SILVEIRA, JULIANO COELHO; CESAR DE ANDRADE, ANDRE FURUGEN; AMBROSIO, CARLOS EDUARDO; et al. Generation and miRNA Characterization of Equine Induced Pluripotent Stem Cells Derived from Fetal and Adult Multipotent Tissues. STEM CELLS INTERNATIONAL, v. 2019, p. 15-pg., 2019-01-01. (14/22887-0, 08/57877-3, 12/50533-2, 15/26818-5, 13/17955-3, 13/08135-2)

JORGE, AMANDA SOARES; RECCHIA, KAIANA; GLORIA, MAYRA HIRAKAWA; DE SOUZA, ALINE FERNANDA; PESSOA, LAIS VICARI DE FIGUEIREDO; NETO, PAULO FANTINATO; MARTINS, DANIELE DOS SANTOS; DE ANDRADE, ANDRE FURUGEN CESAR; MARTINS, SIMONE MARIA MASSAMI KITAMURA; BRESSAN, FABIANA FERNANDES; et al. Porcine Germ Cells Phenotype during Embryonic and Adult Development. ANIMALS, v. 13, n. 15, p. 23-pg., 2023-08-01. (20/10503-3, 15/25564-0, 15/26818-5)

PESSOA, LAIS VICARI DE FIGUEIREDO; BRESSAN, FABIANA FERNANDES; FREUDE, KRISTINE KARLA. Induced pluripotent stem cells throughout the animal kingdom: Availability and applications. WORLD JOURNAL OF STEM CELLS, v. 11, n. 8, p. 491-505, AUG 26 2019. (15/26818-5)

DE CASTRO, RAQUEL V. G.; TAVARES, MARIANA R.; BRESSAN, FABIANA F.; PIERI, NAIRA C. G.; TRINDADE HILL, AMANDA BARACHO; SOUZA, ALINE F.; CRUZ, NATHAN DA R. N.; MARTINS, DANIELE S.; AMBROSIO, CARLOS E.; MEIRELLES, FLAVIO V.; et al. In vitro identification of a stem cell population from canine hair follicle bulge region. TISSUE & CELL, v. 50, p. 43-50, FEB 2018. (15/26818-5)

TRINDADE HILL, AMANDA BARACHO; BRESSAN, FABIANA FERNANDES; MURPHY, BRUCE D.; GARCIA, JOAQUIM MANSANO. Applications of mesenchymal stem cell technology in bovine species. STEM CELL RESEARCH & THERAPY, v. 10, JAN 24 2019. (15/26818-5)

GODOY PIERI, NAIRA CAROLINE; DE SOUZA, ALINE FERNANDA; BOTIGELLI, RAMON CESAR; MACHADO, LUCAS SIMOES; AMBROSIO, CARLOS EDUARDO; MARTINS, DANIELE DOS SANTOS; CESAR DE ANDRADE, ANDRE FURUGEN; MEIRELLES, FLAVIO VIEIRA; HYTTEL, POUL; BRESSAN, FABIANA FERNANDES. Stem cells on regenerative and reproductive science in domestic animals. VETERINARY RESEARCH COMMUNICATIONS, v. 43, n. 1, p. 7-16, FEB 2018. (13/08135-2, 13/09392-9, 12/01060-4, 15/26818-5)

CURCIO, ALINNE GLORIA; BRESSAN, FABIANA FERNANDES; MEIRELLES, FLYVIO VIEIRA; BURLA DIAS, ANGELO JOSE. Achievements and perspectives in cloned and transgenic cattle production by nuclear transfer: influence of cell type, epigenetic status and new technology. ANIMAL REPRODUCTION, v. 14, n. 4, p. 1003-1013, OCT-DEC 2017. (15/26818-5)

GODOY PIERI, NAIRA CAROLINE; DE SOUZA, ALINE FERNANDA; BOTIGELLI, RAMON CESAR; DE FIGUEIREDO PESSOA, LAIS VICARI; RECCHIA, KAIANA; MACHADO, LUCAS SIMOES; GLORIA, MAYRA HIRAKAWA; GUIMARAES DE CASTRO, RAQUEL VASCONCELOS; LEAL, DIEGO FEITOSA; NETO, PAULO FANTINATO; et al. Porcine Primordial Germ Cell-Like Cells Generated from Induced Pluripotent Stem Cells Under Different Culture Conditions. STEM CELL REVIEWS AND REPORTS, v. 18, n. 5, p. 18-pg., 2021-06-11. (13/08135-2, 15/26818-5, 15/25564-0, 17/14884-9)

SANGUINET, EDUARDO DE O.; SIQUEIRA, NATALY M.; MENEZES, FELIPE DE C.; RASIA, GISELE M.; LOTHHAMMER, NIVIA; SOARES, ROSANE M. D.; MEIRELLES, FLAVIO V.; BRESSAN, FABIANA F.; BOS-MIKICH, ADRIANA. Interaction of fibroblasts and induced pluripotent stem cells with poly(vinyl alcohol)-based hydrogel substrates. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, JUN 2019. (15/26818-5, 13/08135-2)

DE FIGUEIREDO PESSOA, LAIS VICARI; LISBOA PIRES, PEDRO RATTO; DEL COLLADO, MAITE; GODOY PIERI, NAIRA CAROLINE; RECCHIA, KAIANA; SOUZA, ALINE FERNANDA; PERECIN, FELIPE; DA SILVEIRA, JULIANO COELHO; CESAR DE ANDRADE, ANDRE FURUGEN; AMBROSIO, CARLOS EDUARDO; et al. Generation and miRNA Characterization of Equine Induced Pluripotent Stem Cells Derived from Fetal and Adult Multipotent Tissues. STEM CELLS INTERNATIONAL, 2019. (08/57877-3, 13/17955-3, 15/26818-5, 13/08135-2, 12/50533-2, 14/22887-0)

GODOY PIERI, NAIRA CAROLINE; DE SOUZA, ALINE FERNANDA; BOTIGELLI, RAMON CESAR; DE FIGUEIREDO PESSOA, LAIS VICARI; RECCHIA, KAIANA; MACHADO, LUCAS SIMOES; GLORIA, MAYRA HIRAKAWA; GUIMARAES DE CASTRO, RAQUEL VASCONCELOS; LEAL, DIEGO FEITOSA; NETO, PAULO FANTINATO; et al. Porcine Primordial Germ Cell-Like Cells Generated from Induced Pluripotent Stem Cells Under Different Culture Conditions. STEM CELL REVIEWS AND REPORTS, JUN 2021. (13/08135-2, 15/26818-5, 15/25564-0, 17/14884-9)

BRESSAN, FABIANA FERNANDES; BASSANEZZE, VINICIUS; DE FIGUEIREDO PESSOA, LAIS VICARI; SACRAMENTO, CHESTER BITTENCOURT; MALTA, TATHIANE MAISTRO; KASHIMA, SIMONE; FANTINATO NETO, PAULO; STREFEZZI, RICARDO DE FRANCISCO; GODOY PIERI, NAIRA CAROLINE; KRIEGER, JOSE EDUARDO; et al. Generation of induced pluripotent stem cells from large domestic animals. STEM CELL RESEARCH & THERAPY, v. 11, n. 1, JUN 25 2020. (15/26818-5, 11/08376-4, 09/11631-6, 13/13686-8, 13/08135-2)

BESSI, BRENDON WILLIAN; BOTIGELLI, RAMON CESAR; PIERI, NAIRA CAROLINE GODOY; MACHADO, LUCAS SIMOES; CRUZ, JESSICA BRUNHARA; DE MORAES, PAMELA; DE SOUZA, ALINE FERNANDA; RECCHIA, KAIANA; BARBOSA, GABRIELA; DE CASTRO, RAQUEL VASCONCELOS GUIMARAES; et al. Cattle In Vitro Induced Pluripotent Stem Cells Generated and Maintained in 5 or 20% Oxygen and Different Supplementation. CELLS, v. 10, n. 6, JUN 2021. (15/26818-5, 19/10751-0, 16/16841-2, 12/50533-2, 18/24520-7)

MACHADO, LUCAS SIMOES; PIERI, NAIRA CAROLINE GODOY; BOTIGELLI, RAMON CESAR; DE CASTRO, RAQUEL VASCONCELOS GUIMARAES; DE SOUZA, ALINE FERNANDA; BRIDI, ALESSANDRA; LIMA, MARINA AMARO; FANTINATO NETO, PAULO; PESSOA, LAIS VICARI DE FIGUEIREDO; MARTINS, SIMONE MARIA MASSAMI KITAMURA; et al. Generation of neural progenitor cells from porcine-induced pluripotent stem cells. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, v. 14, n. 12, NOV 2020. (17/13973-8, 15/26818-5, 13/08135-2, 17/02159-8)

SANGUINET, EDUARDO DE O.; SIQUEIRA, NATALY M.; MENEZES, FELIPE DE C.; RASIA, GISELE M.; LOTHHAMMER, NIVIA; SOARES, ROSANE M. D.; MEIRELLES, FLAVIO V.; BRESSAN, FABIANA F.; BOS-MIKICH, ADRIANA. Interaction of fibroblasts and induced pluripotent stem cells with poly(vinyl alcohol)-based hydrogel substrates. JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, v. 108, n. 3, p. 857-867, APR 2020. (15/26818-5, 13/08135-2)

MACHADO, LUCAS SIMOES; RECCHIA, KAIANA; GODOY PIERI, NAIRA CAROLINE; BOTIGELLI, RAMON CESAR; GUIMARAES DE CASTRO, RAQUEL VASCONCELOS; CRUZ, JESSICA BRUNHARA; DE FIGUEIREDO PESSOA, LAIS VICARI; BRESSAN, FABIANA FERNANDES. Differentiation of Porcine Induced Pluripotent Stem Cells (piPSCs) into Neural Progenitor Cells (NPCs). JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 172, JUN 2021. (17/13973-8, 15/26818-5, 17/02159-8)

DE SOUZA, ALINE FERNANDA; BRESSAN, FABIANA FERNANDES; PIERI, NAIRA CAROLINE GODOY; BOTIGELLI, RAMON CESAR; REVAY, TAMAS; HADDAD, SIMONE KASHIMA; COVAS, DIMAS TADEU; RAMOS, ESTER SILVEIRA; KING, WILLIAN ALLAN; MEIRELLES, FLAVIO VIEIRA. Generation of Primordial Germ Cell-like Cells from iPSCs Derived from Turner Syndrome Patients. CELLS, v. 10, n. 11, NOV 2021. (19/08346-0, 14/50947-7, 17/12140-2, 13/08135-2, 15/26818-5)