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-dependent Coordination of Mouse Cardiac Progenitor Cell Patterning and Differentiation

Abstract

Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of in the anterior SHF results in hypoplastic right ventricle. Activation of in embryonic stem cells arrests cardiac differentiation, whereas -deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both and its paralog results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

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References
1.
Zhou L, Liu J, Olson P, Zhang K, Wynne J, Xie L . Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle progression for cardiac septation. J Mol Cell Cardiol. 2015; 85:1-12. PMC: 4530064. DOI: 10.1016/j.yjmcc.2015.05.005. View

2.
Bertrand N, Roux M, Ryckebusch L, Niederreither K, Dolle P, Moon A . Hox genes define distinct progenitor sub-domains within the second heart field. Dev Biol. 2011; 353(2):266-74. PMC: 3115524. DOI: 10.1016/j.ydbio.2011.02.029. View

3.
Sirbu I, Zhao X, Duester G . Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway. Dev Dyn. 2008; 237(6):1627-35. PMC: 2614402. DOI: 10.1002/dvdy.21570. View

4.
Anders S, Pyl P, Huber W . HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics. 2014; 31(2):166-9. PMC: 4287950. DOI: 10.1093/bioinformatics/btu638. View

5.
Lescroart F, Mohun T, Meilhac S, Bennett M, Buckingham M . Lineage tree for the venous pole of the heart: clonal analysis clarifies controversial genealogy based on genetic tracing. Circ Res. 2012; 111(10):1313-22. DOI: 10.1161/CIRCRESAHA.112.271064. View