Journal ArticleDOI
Human cardiovascular progenitor cells develop from a KDR + embryonic-stem-cell-derived population
Lei Yang,Mark H. Soonpaa,Eric Adler,Torsten K. Roepke,Steven J. Kattman,Marion Kennedy,Els Henckaerts,Kristina Bonham,Geoffrey W. Abbott,R. Michael Linden,R. Michael Linden,Loren J. Field,Gordon Keller,Gordon Keller +13 more
Reads0
Chats0
TLDR
Analysis of the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures identifies a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.Abstract:
The functional heart is comprised of distinct mesoderm-derived lineages including cardiomyocytes, endothelial cells and vascular smooth muscle cells. Studies in the mouse embryo and the mouse embryonic stem cell differentiation model have provided evidence indicating that these three lineages develop from a common Flk-1(+) (kinase insert domain protein receptor, also known as Kdr) cardiovascular progenitor that represents one of the earliest stages in mesoderm specification to the cardiovascular lineages. To determine whether a comparable progenitor is present during human cardiogenesis, we analysed the development of the cardiovascular lineages in human embryonic stem cell differentiation cultures. Here we show that after induction with combinations of activin A, bone morphogenetic protein 4 (BMP4), basic fibroblast growth factor (bFGF, also known as FGF2), vascular endothelial growth factor (VEGF, also known as VEGFA) and dickkopf homolog 1 (DKK1) in serum-free media, human embryonic-stem-cell-derived embryoid bodies generate a KDR(low)/C-KIT(CD117)(neg) population that displays cardiac, endothelial and vascular smooth muscle potential in vitro and, after transplantation, in vivo. When plated in monolayer cultures, these KDR(low)/C-KIT(neg) cells differentiate to generate populations consisting of greater than 50% contracting cardiomyocytes. Populations derived from the KDR(low)/C-KIT(neg) fraction give rise to colonies that contain all three lineages when plated in methylcellulose cultures. Results from limiting dilution studies and cell-mixing experiments support the interpretation that these colonies are clones, indicating that they develop from a cardiovascular colony-forming cell. Together, these findings identify a human cardiovascular progenitor that defines one of the earliest stages of human cardiac development.read more
Citations
More filters
Journal ArticleDOI
Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling
Xiaojun Lian,Cheston Hsiao,Gisela F. Wilson,Kexian Zhu,Laurie B. Hazeltine,Samira M. Azarin,Kunil K. Raval,Kunil K. Raval,Jianhua Zhang,Jianhua Zhang,Timothy J. Kamp,Timothy J. Kamp,Sean P. Palecek +12 more
TL;DR: It is shown that temporal modulation of Wnt signaling is both essential and sufficient for efficient cardiac induction in hPSCs under defined, growth factor-free conditions.
Journal ArticleDOI
Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β-catenin signaling under fully defined conditions
Xiaojun Lian,Jianhua Zhang,Samira M. Azarin,Kexian Zhu,Laurie B. Hazeltine,Xiaoping Bao,Cheston Hsiao,Timothy J. Kamp,Sean P. Palecek +8 more
TL;DR: Functional human cardiomyocytes differentiated via these protocols may constitute a potential cell source for heart disease modeling, drug screening and cell-based therapeutic applications.
Journal ArticleDOI
Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells
Jianhua Zhang,Gisela F. Wilson,Andrew G. Soerens,Chad H. Koonce,Junying Yu,Sean P. Palecek,James A. Thomson,Timothy J. Kamp +7 more
TL;DR: It is concluded that human iPS cells are a viable option as an autologous cell source for cardiac repair and a powerful tool for cardiovascular research.
Journal ArticleDOI
Chemically defined generation of human cardiomyocytes
Paul W. Burridge,Elena Matsa,Praveen K. Shukla,Ziliang C Lin,Jared M. Churko,Antje D. Ebert,Feng Lan,Sebastian Diecke,Bruno C. Huber,Nicholas M. Mordwinkin,Jordan R. Plews,Oscar J. Abilez,Bianxiao Cui,Joseph D. Gold,Joseph C. Wu +14 more
TL;DR: This work systematically developed an optimized cardiac differentiation strategy, using a chemically defined medium consisting of just three components: the basal medium RPMI 1640, L-ascorbic acid 2-phosphate and rice-derived recombinant human albumin, which was effective in 11 hiPSC lines tested.
Journal ArticleDOI
Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines.
Steven J. Kattman,Alec D. Witty,Alec D. Witty,Mark Gagliardi,Nicole Dubois,Maryam Niapour,Akitsu Hotta,James Ellis,Gordon Keller +8 more
TL;DR: It is found that individual mouse and human pluripotent stem cell lines require optimization of these signaling pathways for efficient cardiac differentiation, illustrating a principle that may well apply in other contexts.
References
More filters
Journal ArticleDOI
Cardiomyocytes derived from human embryonic stem cells in pro-survival factors enhance function of infarcted rat hearts
Michael A. Laflamme,Kent Chen,Anna V. Naumova,Veronica Muskheli,James A. Fugate,Sarah K. Dupras,Hans Reinecke,Chunhui Xu,Mohammad Hassanipour,Chris O'Sullivan,Lila R. Collins,Yinhong Chen,Elina Minami,Edward A. Gill,Shuichi Ueno,Chun Yuan,Joseph K. Gold,Charles E. Murry +17 more
TL;DR: This work generated highly purified human cardiomyocytes using a readily scalable system for directed differentiation that relies on activin A and BMP4, and identified a cocktail of pro-survival factors that limitsCardiomyocyte death after transplantation.
Journal ArticleDOI
Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse.
TL;DR: Results provide direct genetic evidence that BMP-4 is essential for several different processes in early mouse development, beginning with gastrulation and mesoderm formation.
Journal ArticleDOI
Isl1 Identifies a Cardiac Progenitor Population that Proliferates Prior to Differentiation and Contributes a Majority of Cells to the Heart
Chen-Leng Cai,Xingqun Liang,Yunqing Shi,Po Hsien Chu,Samuel L. Pfaff,Ju Chen,Sylvia M. Evans +6 more
TL;DR: Two sets of cardiogenic precursors are defined, one of which expresses and requires Isl1 and the other of which does not, which have implications for the development of specific cardiac lineages, left-right asymmetry, cardiac evolution, and isolation of cardiac progenitor cells.
Journal ArticleDOI
Multipotent Embryonic Isl1+ Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification
Alessandra Moretti,Leslie Caron,Atsushi Nakano,Jason T. Lam,Jason T. Lam,Alexandra Bernshausen,Yinhong Chen,Yibing Qyang,Lei Bu,Mika Sasaki,Silvia Martin-Puig,Yunfu Sun,Sylvia M. Evans,Karl-Ludwig Laugwitz,Karl-Ludwig Laugwitz,Kenneth R. Chien +15 more
TL;DR: These studies document a developmental paradigm for cardiogenesis, where muscle and endothelial lineage diversification arises from a single cell-level decision of a multipotent isl1(+) cardiovascular progenitor cell (MICP).
Journal ArticleDOI
Human cardiac stem cells
Claudia Bearzi,Marcello Rota,Toru Hosoda,Jochen Tillmanns,Angelo Nascimbene,Antonella De Angelis,Saori Yasuzawa-Amano,Irina Trofimova,Robert W. Siggins,Nicole LeCapitaine,Stefano Cascapera,Antonio Paolo Beltrami,David A. D'Alessandro,Elias Zias,Federico Quaini,Konrad Urbanek,Robert E. Michler,Roberto Bolli,Jan Kajstura,Annarosa Leri,Piero Anversa +20 more
TL;DR: The identification in vitro of a class of human c-kit-positive cardiac cells that possess the fundamental properties of stem cells: they are self-renewing, clonogenic, and multipotent is reported.