Welcome to the
Stem Cells and Cardiovascular Development Laboratory


 

Palpant Laboratory Centre for Cardiac & Vascular Biology


 

Palpant Laboratory

 

 

 

 

 

 

 

  • Palpant laboratory hESC cardiac cells
     
    hESC-derived cardiomyocytes stained with DAPI (blue), alpha-actinin (green) and an endogenous tdTomato fluorophore expressed from the HOPX locus (red)
  • Palpant laboratory hESC derived endocardial ECs
     
    hESC-derived endocardial ECs seeded into an engineered microvascular network and stained with DAPI (blue) and CD31 (red)
    Read more

The heart, vasculature and blood, which all originate from embryonic mesoderm, together make up the earliest system to form completely in the embryo, providing a functional circulation to support broader organ development during embryogenesis. How the heart, vasculature and blood develop from a common embryonic origin remains poorly understood. In recent years, bioengineering and biotechnology approaches have emerged for studying complex developmental processes with high resolution and precision. Understanding how cell fate choices are controlled during development will help us delve into the basis of congenital and acquired cardiovascular diseases and enable us to make high purity cell types from stem cells that can be used for therapeutic applications.


The Stem Cells and Cardiovascular Development Laboratory, led by Dr Nathan Palpant, is located at the Institute for Molecular Bioscience.  Our research aims to understand how cell fate choices are made during the early stages of cardiovascular development. We use human pluripotent stem cells coupled with advanced techniques in bioengineering, genome engineering and deep sequencing to dissect the molecular basis of lineage choices. The goals of the laboratory are to elucidate the genetic basis of cardiovascular development, use chromatin to understand epigenetic changes governing cell fate choices, identify novel approaches to direct cardiovascular lineage differentiation from pluripotency using small molecules, and using stem cells for cardiovascular disease modelling and therapy.
 

The Palpant Lab

  • 36

    Publications

  • 1175

    Citations

  • 5

    Researchers

  • 4

    Projects

Palpant Laboratory Research

Palpant Laboratory, image shows the ineage decisions made during cardiovascular development



The scope of the lab focuses on using human pluripotent stem cells as a simplified model system of development to provide us with unique approaches for studying formation of the cardiovascular system. Our current work focuses on understanding the mechanisms of cell lineage decisions into cardiomyocytes (heart muscle cells), endocardial endothelial cells (cells that line the inner chamber of the heart and give rise to the valves), as well as the hemogenic endothelium (cells that give rise to the blood and vasculature of the body).

 

Image (right) shows lineage decisions during cardiovascular development.

 

 

 

 

 

Palpant Laboratory, bionics

Stem Cells in Cardio-Respiratory Critical Care

According to current global burden of disease metrics, cardiovascular diseases contribute to 22% of deaths in Australia and costs our healthcare systems in excess of $1 billion pa. In collaboration with Prof John Fraser who heads up the Critical Care Research Group at the Prince Charles Hospital, we are establishing a program to elucidate new knowledge about cardio-respiratory diseases, develop novel point-of-care diagnostics, and advance new therapeutics involving stem cells and mechanical assist devices.

 

 

 

 




Chromatin Dynamics Underlying Cell Identity Genes

Differential methylation and acetylation at specific amino acid residues on histones has emerged as a central mechanism for identifying functionally distinct parts of the genome including promoters, enhancers, open/closed regions of the genome, transcriptionally active DNA and more. My lab studies chromatin dynamics in cardiovascular development as a means to understand how changes in the nucleus translate to changes in cell fate and use unbiased bioinformatics algorithms that analyze chromatin states to identify genes governing cell identity.

Palpant Laboratory chromatin dynamics during cardiovascular development

 

Image (above) shows chromatin deposition of H3K4me3 and H3K27me3 as well as RNA-seq data for cardiac progenitor cells, endocardial ECs and hemogenic ECs. Key loci involved in cell fate and function are shown.

 

 

 

The Genetic Basis of Cardiovascular Development

The mechanisms by which cells navigate developmental pathways into specific tissues requires the complex orchestration of transcriptional changes that ultimately give rise to the functional identity of a cell. My lab focuses on studying novel genetic regulators governing the identity of cells in the cardiovascular system. Understanding the genetics of cell identity is an essential part of learning how to manipulate cell states. We can use this knowledge to enhance tissue regenerative approaches, learn how to enrich cell subtypes from stem cells, and study the basis of developmental diseases. Image shows tmem88 expression during zebrafish development. Tmem88 was identified as a novel regulator of heart development that controls the Wnt/β-catenin signaling pathway.

 

Palpant Laboratory, image shows TMEM88 gene expression in zebrafish

 

Image (left) from Palpant et al. Development, 2013.

 

Palpant NJ. Pabon L. Rabinowitz JS, Stoick-Cooper C, Paige SL, Moon RT, Murry CE. Transmembrane protein 88: a Wnt regulatory protein that specifies cardiovascular progenitor cell fate. Development. 2013 Sep;140(18):3799-808.

 

Read the article

 

 

 

 

 

 

 

 

Palpant Laboratory, stem cell differentiation protocol outline

Methodological Advances in Stem Cell Differentiation Protocols

Developmental biology has formed the groundwork for defining differentiation protocols from pluripotency. Efficient differentiation protocols are required to generate the diverse array of cell types represented in the body either for therapeutic purposes or to understand the basis of complex tissue formation and disease etiology. My lab uses computational approaches in combination with insights from developmental biology to identify simple and efficient methods for deriving cardiovascular cell lineages from pluripotency. One major issue in the field currently is the derivation of cell subtypes (e.g. atrial vs ventricular heart cells or endocardial vs hemogenic endothelium) which is a key area of focus in my lab.

 

Image (right) illustrates the protocol outline (Palpant et al, Development 2015 and Palpant et al, Nature Protocols In press)

 

Palpant NJ*, Pabon L*, Roberts M, Hadland B, Jones D, Jones C, Moon R, Ruzzo W, Bernstein I, Zheng Y, Murry CE. Inhibition of β-catenin signaling re-specifies anterior-like endothelium into beating human cardiomyocytes. Development. 2015 Sep 15;142(18):3198-209.
 

 

 

Palpant NJ, Pabon L, Friedman CE, Roberts M, Hadland B, Zaunbrecher RJ, Bernstein I, Zheng Y, Murry CE. Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nature Protocols. 2017 Jan;12(1):15-31.

Read the Nature Protocols article

 

 

 

 


PROJECTS

 

  • Stem cells in cardio-respiratory critical care

  • Chromatin dynamics underlying cell identity genes

  • The genetic basis of cardiovascular development

  • Methodological advances in stem cell differentiation protocols

 


FUNDING


 

Understanding the differentiation of the endocardium
2017-2020, ARC Discovery Project Grant
Collaborators: Dr Kelly Smith, Dr Nathan Palpant

 

Mechanisms underlying cell fate choices in cardiovascular development
2015-2018, Stem Cells Australia

 


Bionics: Integrating stem cell biologics with critical care research
Queensland Health

 

 

 


NATIONAL COLLABORATIONS

 

Mat Francois
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, the University of Queensland, AUSTRALIA
Cardiovascular development
 

Ben Hogan
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, the University of Queensland, AUSTRALIA
Cardiovascular development
 

Kelly Smith
Division of Genomics of Development and Disease, Institute for Molecular Bioscience, the University of Queensland, AUSTRALIA
Cardiovascular development
 


INTERNATIONAL COLLABORATIONS

 

Yulian Wang
Computational Biology Program, Department of Biomedical Engineering, Oregon Health Sciences University, USA
Analysis of chromatin dynamics and gene expression in mesoderm progenitor populations
 

Jonathan Epstein
Cell and Developmental Biology, University of Pennsylvania, USA
Analysis of HOPX in developmental hematopoiesis
 

Irwin Bernstein
Fred Hutchinson Cancer Research Center, USA
Analysis of hematopoietic potential from hESC-derived endothelial populations

 

 

Palpant Lab UQ Centre for Cardiac Vascular Biology

The Palpant Lab - Nathan Palpant, Han Sheng Chiu and Clayton Friedman

 

 

 

 

Palpant lab public presentations, media and press releases


TELEVISION AND MEDIA REPORTS

1 Nov 2016     IMB News
$4.5 million for IMB-led discovery research
UQ Centre for Cardiac and Vascular Biology research teams led by Dr Kelly Smith and Dr Nathan Palpant have been awarded funding by the Australian Research Council for a groundbreaking new discovery research project, 'Understanding the differentiation of the endocardium". UQ CCVB News

 

 

20 Sep 2016
Announcing $1.3 million in grant support from Queensland Health for a new research collaboration between Dr Palpant's team at the Institute for Molecular Bioscience and Professor John Fraser and the Critical Care Research Group at the Prince Charles Hospital. The new research project, developing novel treatments for heart attack, stroke and heart disease, aired on Channel 10 News and was broadcast on ABC radio.


Channel Ten Australia logoChannel 10 News
Bionic heart and lung research gets million dollar injection
Brisbane scientists and engineers have welcomed a $1.3 million government grant to help them develop the vital technology.

 

 



PUBLIC PRESENTATIONS

24 Feb 2017  From broken to bionic: How medical breakthroughs are repairing hearts
Dr Palpant presents in the Health Matters public lecture series. Featuring world-renowned researchers and clinicians, this lecture will discuss how modern mechanics and heart muscle regeneration are keeping hearts beating.
Health Matters Lecture, Faculty of Medicine, UQ

Read the UQ CCVB blog article

 

30 Aug 2016   Using chromatin dynamics to identify genes governing cell states
Dr Palpant presented on using chromatin dynamics to identify genes governing cell states at the Society for Reproductive Biology Annual Symposium.
Australian Patient Education

 

 

 

 

Palpant Laboratory publications

 

 

Palpant NJ, Pabon L, Friedman CE, Roberts M, Hadland B, Zaunbrecher RJ, Bernstein I, Zheng Y, Murry CE. Generating high-purity cardiac and endothelial derivatives from patterned mesoderm using human pluripotent stem cells. Nature Protocols. 2017 Jan;12(1):15-31.
 

Szabo L, Morey R, Palpant NJ, Wang PL, Afari N, Jiang C, Parast MM, Murry CE, Laurent LC, Salzman J. Tissue-specific induction of circular RNA during human fetal development revealed by statistically based splicing detection. Genome Biology. 2015 Jun 16;16(1):126.
 

Palpant NJ*, Pabon L*, Roberts M, Hadland B, Jones D, Jones C, Moon R, Ruzzo W, Bernstein I, Zheng Y, Murry CE. Inhibition of β-catenin signaling re-specifies anterior-like endothelium into beating human cardiomyocytes. Development. 2015 Sep 15;142(18):3198-209. Read more
 

Szabo L, Morey R, Palpant NJ, Wang PL, Afari N, Jiang C, Parast MM, Murry CE, Laurent LC; Salzman J. Tissue-specific induction of circular RNA during human fetal development revealed by statistically based splicing detection. Genome Biology. 2015 Jun 16;16(1):126.
 

Palpant NJ, Hofsteen P, Pabon L, Reinecke H, Murry CE. Cardiac Development in Human Embryonic Stem Cells and Zebrafish is Inhibited by Exposure to Tobacco Cigarettes and E-Cigarettes. PLoS One. 2015 May 15;10(5):e0126259.
 

Zhu WZ, Filice D, Palpant NJ and Laflamme MA. Methods for assessing the electromechanical integration of human pluripotent stem cell-derived cardiomyocyte grafts. Chapter in L. Black and M. Radisic (eds) Cardiac Tissue Engineering Methods and Protocols. Methods Mol Biol. 2014;1181:229-47.
 

Palpant NJ and Murry CE. Proliferation at the Heart of Preadolescence. Cell. 2014 May 8;157(4):765-7.
 

Chong JJ, Yang X, Don CW, Minami E, Liu Y, Weyers JJ, Mahoney WM, Van Biber B, Palpant NJ, Gantz J, Fugate JA, Muskheli V, Gough GM, Vogel KW, Astley CA, Hotchkiss CE, Baldessari A, Pabon L, Reinecke H, Gill EA, Nelson V, Kiem H, Laflamme MA, Murry CE. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts. Nature. 2014 Apr 30.
 

Palpant NJ. Pabon L. Rabinowitz JS, Stoick-Cooper C, Paige SL, Moon RT, Murry CE. Transmembrane protein 88: a Wnt regulatory protein that specifies cardiovascular progenitor cell fate. Development. 2013 Sep;140(18):3799-808.
 

Murry CE, Palpant NJ, Maclellan WR. Cardiopoietry in Motion: Primed Mesenchymal Stem Cells for Ischemic Cardiomyopathy. J Am Coll Cardiol. 2013 Apr 10.
 

Palpant NJ and Dudzinski D. Zinc Finger Nucleases: Looking Toward Translation. Gene Therapy. 2013 Feb;20(2):121-7. doi: 10.1038/gt.2012.2. Epub 2012 Feb 9.
 

Gantz J*, Palpant NJ*, Welikson RE, Hauschka SD. Murry CE, Laflamme M. Targeted genomic integration of a selectable floxed dual fluorescence reporter in human embryonic stem cells. PLoS One. 2012;7(10):e46971, Epub 2012 Oct 10.
 

Shiba Y, Fernandes S, Zhu W, Kim J, Palpant NJ, Gantz J, Moyes KW, Muskheli V, Reinecke H, Van Biber B, Dardas T, Mignone JL, Izawa A, Hanna R, Viswanathan M, Gold JD, Kotlikoff MI, Murry CE, Laflamme MA. Human ESC-Derived Cardiomyocytes Electrically Integrate and Suppress Arrhythmias in a Guinea Pig Infarct Model. Nature. 2012 Sep 13;489(7415):322-5.
 

Davis J, Yasuda S, Palpant NJ, Martindale J, Stevenson T, Converso K, Metzger JM. Diastolic dysfunction and thin filament dysregulation resulting from excitation–contraction uncoupling in a mouse model of restrictive cardiomyopathy. Journal of Molecular and Cellular Cardiology. J Mol Cell Cardiol. 2012 Sep;53(3):446-57.
 

Palpant NJ, Murry CE. Regenerative medicine: Reprogramming the injured heart. Nature. 2012 May 31;485(7400):585-6.
 

Palpant NJ, Houang EM, Sham YY, Metzger JM. pH responsive titratable inotropic performance of histidine-modified cardiac troponin I. Biophysical Journal. 2012 Apr 4;102(7):1570-9.
 

Palpant NJ, Bedada FB, Peacock B, Blazar BR, Metzger JM, Tolar J. Cardiac disease in mucopolysaccharidosis type I attributed to catecholaminergic and hemodynamic deficiencies. American Journal of Physiology – Heart and Circulatory Physiology. 2011 Jan;300(1):H356- 65.
 

Barnabei M, Palpant NJ, Metzger JM. Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains. Physiological Genomics. 2010 Sep;42A(2):103-13.
 

Palpant NJ, Houang EM, Delport W, Hastings KEM, Unofriev AV, Sham YY, and Metzger JM. Pathogenic peptide deviations support a model of adaptive evolution of chordate cardiac performance by troponin mutations. Physiological Genomics. 2010 Jul 7;42(2):287-99.
 

Palpant NJ, Metzger JM. Aesthetic Cardiology: adipose-derived stem cells for myocardial repair. Current Stem Cell Research and Therapy. 2010 Jun;5(2):145-52.
 

Palpant NJ, Szatkowski ML, Townsend D, Wang W, Koch LG, Britton SL, Metzger JM. Artificial Selection for Whole Animal Low Intrinsic Aerobic Capacity Co-Segregates with Hypoxia-Induced Cardiac Pump Failure. PLoS One. 2009 Jul 1;4(7):e6117.
 

Palpant NJ, D’Alecy LG, Metzger JM. Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo. The FASEB Journal. 2009 May;23(5):1529-40.
 

Turner II, Wang W, Townsend D, Palpant NJ, Bedada F, Fomicheva EV, Metzger JM. Molecular cardiology in translation: gene, cell and chemical-based experimental therapeutics for the failing heart. Journal of Translational Cardiovascular Research. 2008; 1:317-327.
 

Palpant NJ, Day SM, Herron TJ, Metzger JM. Single histidine substituted cardiac troponin I confers protection from age-related systolic and diastolic dysfunction. Cardiovascular Research. 2008 Nov 1;80(2):209-18.
 

Palpant NJ, Yasuda S, MacDougald OA, Metzger JM. Non-canonical Wnt signaling enhances differentiation of Sca1+/c-kit+ adipose-derived murine stromal vascular cells into spontaneously beating cardiac myocytes. Journal of Molecular and Cellular Cardiology. 2007 Sep;43(3):362-70.

 

 

REVIEWS AND COMMENTARIES

 

Nakano A, Nakano H, Smith K, Palpant NJ. The developmental origins and lineage contributions of endocardial endothelium. Biochim Biophys Acta. 2016 Jan 29. pii: S0167-4889(16)30012-X. doi: 10.1016/j.bbamcr.2016.01.022.

 

Zhu WZ, Filice D, Palpant NJ and Laflamme MA.  Methods for assessing the electromechanical integration of human pluripotent stem cell-derived cardiomyocyte grafts. Chapter in L. Black and M. Radisic (eds) Cardiac Tissue Engineering Methods and Protocols. Methods Mol Biol. 2014;1181:229-47.

 

Palpant NJ and Murry CE. Proliferation at the Heart of Preadolescence. Cell. 2014 May 8;157(4):765-7.

 

Murry CE, Palpant NJ, Maclellan WR. Cardiopoietry in Motion: Primed Mesenchymal Stem Cells for Ischemic Cardiomyopathy. J Am Coll Cardiol. 2013 Apr 10.

 

Palpant NJ and Dudzinski D. Zinc Finger Nucleases: Looking Toward Translation. Gene Therapy. 2013 Feb;20(2):121-7. doi: 10.1038/gt.2012.2. Epub 2012 Feb 9.

 

Palpant NJ, Murry CE. Regenerative medicine: Reprogramming the injured heart. Nature. 2012 May 31;485(7400):585-6.

 

Palpant NJ, Metzger JM. Aesthetic Cardiology: adipose-derived stem cells for myocardial repair. Current Stem Cell Research and Therapy. 2010 Jun;5(2):145-52.

 

Turner II, Wang W, Townsend D, Palpant NJ, Bedada F, Fomicheva EV, Metzger JM. Molecular cardiology in translation: gene, cell and chemical-based experimental therapeutics for the failing heart. Journal of Translational Cardiovascular Research. 2008; 1:317-327.

 

BOOKS

 

Ronald Green (Editor) and Nathan Palpant (Editor). Suffering and Bioethics. Oxford University Press. 2014.

Steve Dilley (Editor) and Nathan Palpant (Editor). Human Dignity and Bioethics: from worldviews to the public square. Annals of Bioethics. Routledge. 2013.


BOOK CHAPTERS

 

Palpant NJ. Suffering and Ethics in an Age of Empowerment. In: Suffering and Bioethics. Nathan Palpant (Editor) and Ronald Green (Editor). Oxford University Press. 2014.

Palpant NJ and Holland S. Human Dignity in the Human Embryonic Stem Cell Controversy. In: Human Dignity and Bioethics: from worldviews to the public square. Nathan Palpant (Editor) and Steve Dilley (Editor). Routledge. 2013.