Related Experiment Video
Updated: May 10, 2026

Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
Published on: February 17, 2015
Embryonic stem cell-derived CD166+ precursors develop into fully functional sinoatrial-like cells
Angela Scavone1, Daniela Capilupo, Nausicaa Mazzocchi
1Department of Biosciences, Università degli Studi di Milano, Milano, Italy.
Rationale:
A cell-based biological pacemaker is based on the differentiation of stem cells and the selection of a population displaying the molecular and functional properties of native sinoatrial node (SAN) cardiomyocytes. So far, such selection has been hampered by the lack of proper markers. CD166 is specifically but transiently expressed in the mouse heart tube and sinus venosus, the prospective SAN.
Objective:
We have explored the possibility of using CD166 expression for isolating SAN progenitors from differentiating embryonic stem cells.
Methods And Results:
We found that in embryonic day 10.5 mouse hearts, CD166 and HCN4, markers of the pacemaker tissue, are coexpressed. Sorting embryonic stem cells for CD166 expression at differentiation day 8 selects a population of pacemaker precursors. CD166+ cells express high levels of genes involved in SAN development (Tbx18, Tbx3, Isl-1, Shox2) and function (Cx30.2, HCN4, HCN1, CaV1.3) and low levels of ventricular genes (Cx43, Kv4.2, HCN2, Nkx2.5). In culture, CD166+ cells form an autorhythmic syncytium composed of cells morphologically similar to and with the electrophysiological properties of murine SAN myocytes. Isoproterenol increases (+57%) and acetylcholine decreases (-23%) the beating rate of CD166-selected cells, which express the β-adrenergic and muscarinic receptors. In cocultures, CD166-selected cells are able to pace neonatal ventricular myocytes at a rate faster than their own. Furthermore, CD166+ cells have lost pluripotency genes and do not form teratomas in vivo.
Conclusions:
We demonstrated for the first time the isolation of a nonteratogenic population of cardiac precursors able to mature and form a fully functional SAN-like tissue.
Related Concept Videos
Development of the Heart
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart tube by...
Source And Potency Of Stem Cells
Production of Formed Elements
Most HSCs commit to...
Multipotency of Hematopoietic Stem Cells
Zygotic Development And Stem Cell Formation
Embryonic Stem Cells

