Identification of surface markers in cardiac precursors of rats

• Grant number: 13/26440-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2014
• End date: December 31, 2014
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: José Eduardo Krieger
• Grantee: Aline Alfonso Keusseyan
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Cardiovascular diseases, such as myocardial infarction, have high mortality rates due to the scarce amount of therapies offered to patients, due to the low regenerative capacity of adult mammalian heart. However, recent evidences surprisingly shows that resected hearts of mice can regenerate completely, even if it is restricted only to the first day of life. It is assumed that this process occurs via cells capable of generating new cardiomyocytes (defined hereafter as cardiac precursors) and there is great interest in identifying them accurately. According to the literature, cardiac precursors are present in both embryonic and adult stage. Traditionally intracellular markers of cardiac development, like Nkx2.5 or genes ISL1 and the contractile machinery genes have been used to identify them. Some surface molecules (Flk-1, c-kit, Sca -1 and MDR -1) are known, but do not are truly specific and may be found in other cell types. In our laboratory, we established the model of resection of the rat heart and the same process of cardiac regeneration was observed. More recently, we did an RNASeq experiment to assess differential expression (DE) genes between resected animals with a day and seven days. Thus, we could identify 34 membrane genes that were overexpressed in animals with one day and 10 of them seem quite interesting. It is of interest to investigate whether any of them work as a more specific marker for heart cells with regenerative capacity.In this project, we aim to verify the hypothesis that any of the 10 candidate genes that were obtained from RNASeq platform serve as a more specific marker for cardiac precursors in neonatal mice that underwent surgical resection (1 day after birth; 1D).The expression of such markers will be compared with other experimental groups, as follows: non-manipulated, resected animals after 7 days after birth and false-operated (SHAM). Furthermore, experiments will be performed in three periods after resection in order to evaluate how these genes behave with time. The discovery of surface markers that promote specific recognition of cardiac precursor cells is highly desirable . This knowledge could identify the cardiac precursors and also be applied as a tool to enrich the population by MACS or FACS, which will be useful for optimizing the process of obtaining cardiomyocytes from iPS cells.

Scientific publications

(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)

TEOFILO SATURI DE CARVALHO, ANA ELISA; BASSANEZE, VINICIUS; FORNI, MARIA FERNANDA; KEUSSEYAN, ALINE ALFONSO; KOWALTOWSKI, ALICIA JULIANA; KRIEGER, JOSE EDUARDO. Early Postnatal Cardiomyocyte Proliferation Requires High Oxidative Energy Metabolism. SCIENTIFIC REPORTS, v. 7, NOV 13 2017. (12/10109-7, 13/17368-0, 13/04871-6, 13/26440-7, 11/19678-1, 15/25776-7, 13/07937-8)