Shenje, Lincoln T and Andersen, Peter and Uosaki, Hideki and Fernandez, Laviel and Rainer, Peter P and Cho, Gun-Sik and Lee, Dong-Ik and Zhong, Weimin and Harvey, Richard P and Kass, David A and Kwon, Chulan (2014) Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors. eLife, 3. pp. e02164. ISSN 2050-084X (OA)
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Abstract
Cardiac progenitor cells (CPCs) must control their number and fate to sustain the rapid heart growth during development, yet the intrinsic factors and environment governing these processes remain unclear. Here, we show that deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs in second pharyngeal arches (PA2s) and is associated with an atrophic heart. With histological, flow cytometric and functional analyses, we find that CPCs remain undifferentiated and expansive in the PA2, but differentiate into cardiac cells as they exit the arch. Tracing of Nb- and Nbl-deficient CPCs by lineage-specific mosaicism reveals that the CPCs normally populate in the PA2, but lose their expansion potential in the PA2. These findings demonstrate that Nb and Nbl are intrinsic factors crucial for the renewal of CPCs in the PA2 and that the PA2 serves as a microenvironment for their expansion. (Grants: NIH, NHLB; No Australian funders listed)
| Item Type: | Article |
|---|---|
| Additional Information: | This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/), which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 22 Jan 2016 00:09 |
| Last Modified: | 30 Jun 2016 00:21 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/221 |
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