Generation of PDGFRα+Cardioblasts from Pluripotent Stem Cells.
Isolating actively proliferating cardioblasts is the first crucial step for cardiac regeneration through cell implantation. However, the origin and identity of putative cardioblasts are still unclear. Here, we uncover a novel class of cardiac lineage cells, PDGFRα+Flk1-cardioblasts (PCBs), from mouse and human pluripotent stem cells induced using CsAYTE, a combination of the small molecules Cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. This novel population of actively proliferating cells is cardiac lineage-committed but in a morphologically and functionally immature state compared to mature cardiomyocytes. Most important, most of CsAYTE-induced PCBs spontaneously differentiated into functional αMHC+cardiomyocytes (M+CMs) and could be a potential cellular resource for cardiac regeneration.
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Seon Pyo
SP
Hong
Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea.
Sukhyun
S
Song
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Sung Woo
SW
Cho
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Seungjoo
S
Lee
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Bong Ihn
BI
Koh
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea.
Hosung
H
Bae
Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea.|Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Kyun Hoo
KH
Kim
Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea.|Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Jin-Sung
JS
Park
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Hyo-Sang
HS
Do
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Ilkyun
I
Im
Cardiovascular and Metabolic Disease Center, Department of Physiology, College of Medicine, Inje University, Busan, Korea.
Hye Jin
HJ
Heo
Cardiovascular and Metabolic Disease Center, Department of Physiology, College of Medicine, Inje University, Busan, Korea.
Tae Hee
TH
Ko
Cardiovascular and Metabolic Disease Center, Department of Physiology, College of Medicine, Inje University, Busan, Korea.
Jae-Hyeong
JH
Park
Cardiovascular and Metabolic Disease Center, Department of Physiology, College of Medicine, Inje University, Busan, Korea.
Jae Boum
JB
Youm
CHA Cancer Institute, Department of Biomedical Science, CHA University, Seoul, Korea.
Seong-Jin
SJ
Kim
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Injune
I
Kim
Cardiovascular and Metabolic Disease Center, Department of Physiology, College of Medicine, Inje University, Busan, Korea.
Jin
J
Han
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Yong-Mahn
YM
Han
Biomedical Science and Engineering Interdisciplinary Program, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, Korea.|Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Gou Young
GY
Koh
D000577:Amides / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
D000577:Amides; D000814:Aniline Compounds; D000975:Antioxidants; D002839:Chromans; D004791:Enzyme Inhibitors; D011725:Pyridines; D014230:Triazoles; C108830:Y 27632; C000590371:vactosertib; D016572:Cyclosporine; D020796:Receptor, Platelet-Derived Growth Factor alpha; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid