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Assay for Small Molecules and Defined Factors to Trigger Renewal of Cardiac Progenitors

详细技术说明

Scientists at UC San Diego have discovered a high-throughput screening assay for identifying a detectably labeled small molecule that modulates cardiac progenitor cells. The invention also describes a method of identifying small molecules from the high-throughput assay affecting cardiogenesis and/or modulating cardiac progenitor cell development. Also provided are methods of stimulating maturation of cardiac progenitor cells using a GSK-3P inhibitor.

*Abstract

The heart is composed of diverse muscle and non-muscle cell lineages. Congenital heart diseases can arise from defects in the pathways for heart lineage specification, and human degenerative diseases can arise in a subset of ventricular and pacemaker cell lineages. The pathways that guide heart-cell lineage diversification are relatively obscure, as the primordial heart precursor cells have not been clearly identified. Two fields of cardiac progenitors have been described; the primary and secondary, or anterior heart fields. The primary heart field is believed to give rise to the atria and ventricles of the heart, while the secondary or anterior field is believed to give rise to the outflow tract. Some cells in the outflow tract originate from splanchnic mesoderm adjacent to the pharyngeal endoderm. Several studies have demonstrated induction of cardiogenic mesoderm in response to inhibition of Wnt signaling in chick, Xenopus, and mouse embryos. Islet1 is the only gene known to date that is specifically expressed in cardiogenic stem cells, but not in differentiated cardiac cells. Islet1 may be a master regulator of the cardiogenic stem-cell state. This discovery enables use of islet1 expression as a means to isolate endogenous cardiogenic stem cells, or to create cardiogenic stem cells.

*IP Issue Date

Dec 4, 2012

*Principal Investigation

Name: Ju Chen

Department:

Name: Kenneth Chien

Department:

Name: Sylvia Evans

Department:

Name: Karl-Ludwig Laugwitz

Department:

Name: Lizhu Lin

Department:

Name: Alessandra Moretti

Department:

Name: Yibing Qyang

Department:

附加资料

Patent Number: US8323909B2
Application Number: US2010770597A
Inventor: Evans, Sylvia | Chen, Ju | Lin, Lizhu | Chien, Ken | Qyang, Yibing | Moretti, Alessandra | Laugwitz, Karl
Priority Date: 2 Feb 2004
Priority Number: US8323909B2
Application Date: 29 Apr 2010
Publication Date: 4 Dec 2012
IPC Current: C12N000500 | G01N003353
US Class: 4350071 | 435375 | 435377
Assignee Applicant: The Regents of the University of California
Title: Methods of identifying small molecules for renewals, survival and migration of cardiac progenitors
Usefulness: Methods of identifying small molecules for renewals, survival and migration of cardiac progenitors
Summary: The assay and methods are useful for identifying a small molecule, which affects or regulates cardiogenesis, high-throughput screening assay, stimulating maturation of cardiac progenitor cells, and for generating an Isl1 lineage-traced cell.
Novelty: Identifying small molecule regulating cardiogenesis by determining islet 1 transcription factor expression in labeled cardiac progenitor cells isolated from transgenic non-human animal having tamoxifen-dependent Cre-recombinase

主要类别

诊断/治疗

细分类别

其他疾病

申请号码

8323909

其他

Intellectual Property Info

U.S. patent application filed 02-May-2007, published on 08-May-2008 (2008/0108090).

Tech ID/UC Case

20035/2006-211-0

Related Cases

2006-211-0

国家/地区

美国