Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors

Lincoln T. Shenje, Peter Andersen, Hideki Uosaki, Laviel Fernandez, Peter P. Rainer, Gun Sik Cho, Dong Ik Lee, Weimin Zhong, Richard P. Harvey, David A. Kass, Chulan Kwon

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.DOI: http://dx.doi.org/10.7554/eLife.02164.001.

Original languageEnglish (US)
Pages (from-to)e02164
JournaleLife
Volume3
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Intrinsic Factor
Arches
Stem Cells
Branchial Region
Mosaicism
Cell Lineage
Growth and Development

Keywords

  • cardiac progenitor
  • heart
  • microenvironment
  • niche
  • numb
  • self-renewal

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shenje, L. T., Andersen, P., Uosaki, H., Fernandez, L., Rainer, P. P., Cho, G. S., ... Kwon, C. (2014). Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors. eLife, 3, e02164. https://doi.org/10.7554/eLife.02164

Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors. / Shenje, Lincoln T.; Andersen, Peter; Uosaki, Hideki; Fernandez, Laviel; Rainer, Peter P.; Cho, Gun Sik; Lee, Dong Ik; Zhong, Weimin; Harvey, Richard P.; Kass, David A.; Kwon, Chulan.

In: eLife, Vol. 3, 2014, p. e02164.

Research output: Contribution to journalArticle

Shenje, LT, Andersen, P, Uosaki, H, Fernandez, L, Rainer, PP, Cho, GS, Lee, DI, Zhong, W, Harvey, RP, Kass, DA & Kwon, C 2014, 'Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors', eLife, vol. 3, pp. e02164. https://doi.org/10.7554/eLife.02164
Shenje LT, Andersen P, Uosaki H, Fernandez L, Rainer PP, Cho GS et al. Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors. eLife. 2014;3:e02164. https://doi.org/10.7554/eLife.02164
Shenje, Lincoln T. ; Andersen, Peter ; Uosaki, Hideki ; Fernandez, Laviel ; Rainer, Peter P. ; Cho, Gun Sik ; Lee, Dong Ik ; Zhong, Weimin ; Harvey, Richard P. ; Kass, David A. ; Kwon, Chulan. / Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors. In: eLife. 2014 ; Vol. 3. pp. e02164.
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