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Article ; Online: Differentiation of monocytes and polarized M1/M2 macrophages from human induced pluripotent stem cells.

Park, Tea Soon / Hirday, Rishabh / Quinn, Russell / Jacob, Sheela Panicker / Feldman, Ricardo A / Bose, Devika / Sharma, Ruchi / Bharti, Kapil

STAR protocols

2024 Volume 5, Issue 1, Page(s) 102827

Abstract: Here, we present a protocol to differentiate induced pluripotent stem cell (iPSC) into adherent hematopoietic progenitors that release floating CD14+ CD45+ monocytes into the culture medium. We describe steps for iPSC expansion, embryoid body (EB) ... ...

Abstract	Here, we present a protocol to differentiate induced pluripotent stem cell (iPSC) into adherent hematopoietic progenitors that release floating CD14+ CD45+ monocytes into the culture medium. We describe steps for iPSC expansion, embryoid body (EB) formation, suspension culture, plating EBs, and recurring harvests of monocytes, a.k.a. "monocyte factory." We then describe detailed procedures for freezing/thawing of monocytes and differentiation into polarized M1 and M2 macrophages. This protocol provides foundation to study iPSC monocytes and their progenies such as macrophages, microglial, and dendritic cells. For complete details on the use and execution of this protocol, please refer to Karlson et al.
MeSH term(s)	Humans ; Monocytes ; Induced Pluripotent Stem Cells ; Macrophages ; Cell Differentiation ; Embryoid Bodies
Language	English
Publishing date	2024-01-13
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102827
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Article ; Online: Protocol to generate endothelial cells, pericytes, and fibroblasts in one differentiation round from human-induced pluripotent stem cells.

Park, Tea Soon / Hirday, Rishabh / Ali, Amir / Megersa, Roba / Villasmil, Rafael / Nguyen, Eric / Bharti, Kapil

STAR protocols

2023 Volume 4, Issue 2, Page(s) 102292

Abstract: Here, we present a protocol for differentiating human-induced pluripotent stem cells into three distinct mesodermal cell types: vascular endothelial cells (ECs), pericytes, and fibroblasts. We describe steps for using monolayer serum-free differentiation ...

Abstract	Here, we present a protocol for differentiating human-induced pluripotent stem cells into three distinct mesodermal cell types: vascular endothelial cells (ECs), pericytes, and fibroblasts. We describe steps for using monolayer serum-free differentiation and isolating ECs (CD31
Language	English
Publishing date	2023-05-06
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2023.102292
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Article ; Online: Generation of Pericytic-Vascular Progenitors from Tankyrase/PARP-Inhibitor-Regulated Naïve (TIRN) Human Pluripotent Stem Cells.

Zimmerlin, Ludovic / Park, Tea Soon / Bhutto, Imran / Lutty, Gerard / Zambidis, Elias T

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2416, Page(s) 133–156

Abstract: Tankyrase/PARP inhibitor-regulated naïve human pluripotent stem cells (TIRN-hPSC) represent a new class of human stem cells for regenerative medicine that can differentiate into multi-lineage progenitors with improved in vivo functionality. Chemical ... ...

Abstract	Tankyrase/PARP inhibitor-regulated naïve human pluripotent stem cells (TIRN-hPSC) represent a new class of human stem cells for regenerative medicine that can differentiate into multi-lineage progenitors with improved in vivo functionality. Chemical reversion of conventional, primed hPSC to a TIRN-hPSC state alleviates dysfunctional epigenetic donor cell memory, lineage-primed gene expression, and potentially disease-associated aberrations in their differentiated progeny. Here, we provide methods for the reversion of normal or diseased patient-specific primed hPSC to TIRN-hPSC and describe their subsequent differentiation into embryonic-like pericytic-endothelial "naïve" vascular progenitors (N-VP). N-VP possess improved vascular functionality, high epigenetic plasticity, maintain greater genomic stability, and are more efficient in migrating to and re-vascularizing ischemic tissues than those generated from primed isogenic hPSC. We also describe detailed methods for the ocular transplantation and quantitation of vascular engraftment of N-VP into the ischemia-damaged neural retina of a humanized mouse model of ischemic retinopathy. The application of TIRN-hPSC-derived N-VP will advance vascular cell therapies of ischemic retinopathy, myocardial infarction, and cerebral vascular stroke.
MeSH term(s)	Animals ; Cell Differentiation/drug effects ; Humans ; Ischemia ; Mice ; Pluripotent Stem Cells ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Retinal Diseases ; Tankyrases
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors ; Tankyrases (EC 2.4.2.30)
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1908-7_10
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Article ; Online: Capturing Human Naïve Pluripotency in the Embryo and in the Dish.

Zimmerlin, Ludovic / Park, Tea Soon / Zambidis, Elias T

Stem cells and development

2017 Volume 26, Issue 16, Page(s) 1141–1161

Abstract: Although human embryonic stem cells (hESCs) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to postimplantation lineage-primed murine epiblast stem cells than to naïve ... ...

Abstract	Although human embryonic stem cells (hESCs) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to postimplantation lineage-primed murine epiblast stem cells than to naïve preimplantation inner cell mass-derived mouse ESCs (mESCs). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESCs and human induced pluripotent stem cells (hiPSCs) appear to lack many of the defining hallmarks of naïve mESCs. These include important features of the naïve ground state murine epiblast, such as an open epigenetic architecture, reduced lineage-primed gene expression, and chimera and germline competence following injection into a recipient blastocyst-stage embryo. Several transgenic and chemical methods were recently reported that appear to revert conventional human PSCs to mESC-like ground states. However, it remains unclear if subtle deviations in global transcription, cell signaling dependencies, and extent of epigenetic/metabolic shifts in these various human naïve-reverted pluripotent states represent true functional differences or alternatively the existence of distinct human pluripotent states along a spectrum. In this study, we review the current understanding and developmental features of various human pluripotency-associated phenotypes and discuss potential biological mechanisms that may support stable maintenance of an authentic epiblast-like ground state of human pluripotency.
MeSH term(s)	Animals ; Blastocyst/cytology ; Blastocyst/metabolism ; Cellular Reprogramming ; Cellular Reprogramming Techniques/methods ; Gene Expression Regulation, Developmental ; Humans ; MAP Kinase Signaling System ; Mice ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism
Language	English
Publishing date	2017-06-26
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2142214-X
ISSN	1557-8534 ; 1547-3287
ISSN (online)	1557-8534
ISSN	1547-3287
DOI	10.1089/scd.2017.0055
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Article ; Online: Chemical Reversion of Conventional Human Pluripotent Stem Cells to a Naïve-like State with Improved Multilineage Differentiation Potency.

Park, Tea Soon / Zimmerlin, Ludovic / Evans-Moses, Rebecca / Zambidis, Elias T

Journal of visualized experiments : JoVE

2018 , Issue 136

Abstract: Naïve human pluripotent stem cells (N-hPSC) with improved functionality may have a wide impact in regenerative medicine. The goal of this protocol is to efficiently revert lineage-primed, conventional human pluripotent stem cells (hPSC) maintained on ... ...

Abstract	Naïve human pluripotent stem cells (N-hPSC) with improved functionality may have a wide impact in regenerative medicine. The goal of this protocol is to efficiently revert lineage-primed, conventional human pluripotent stem cells (hPSC) maintained on either feeder-free or feeder-dependent conditions to a naïve-like pluripotency with improved functionality. This chemical naïve reversion method employs the classical leukemia inhibitory factor (LIF), GSK3β, and MEK/ERK inhibition cocktail (LIF-2i), supplemented with only a tankyrase inhibitor XAV939 (LIF-3i). LIF-3i reverts conventional hPSC to a stable pluripotent state adopting biochemical, transcriptional, and epigenetic features of the human pre-implantation epiblast. This LIF-3i method requires minimal cell culture manipulation and is highly reproducible in a broad repertoire of human embryonic stem cell (hESC) and transgene-free human induced pluripotent stem cell (hiPSC) lines. The LIF-3i method does not require a re-priming step prior to the differentiation; N-hPSC can be differentiated directly with extremely high efficiencies and maintain karyotypic and epigenomic stabilities (including at imprinted loci). To increase the universality of the method, conventional hPSC are first cultured in the LIF-3i cocktail supplemented with two additional small molecules that potentiate protein kinase A (forskolin) and sonic hedgehog (sHH) (purmorphamine) signaling (LIF-5i). This brief LIF-5i adaptation step significantly enhances the initial clonal expansion of conventional hPSC and permits them to be subsequently naïve-reverted with LIF-3i alone in bulk quantities, thus obviating the need for picking/subcloning rare N-hPSC colonies later. LIF-5i-stabilized hPSCs are subsequently maintained in LIF-3i alone without the need of anti-apoptotic molecules. Most importantly, LIF-3i reversion markedly improves the functional pluripotency of a broad repertoire of conventional hPSC by decreasing their lineage-primed gene expression and erasing the interline variability of directed differentiation commonly observed amongst independent hPSC lines. Representative characterizations of LIF-3i-reverted N-hPSC are provided, and experimental strategies for functional comparisons of isogenic hPSC in lineage-primed vs. naïve-like states are outlined.
MeSH term(s)	Cell Culture Techniques ; Cell Differentiation ; Germ Layers/metabolism ; Humans ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Signal Transduction
Language	English
Publishing date	2018-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/57921
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Article ; Online: Elevated glucosylsphingosine in Gaucher disease induced pluripotent stem cell neurons deregulates lysosomal compartment through mammalian target of rapamycin complex 1.

Srikanth, Manasa P / Jones, Jace W / Kane, Maureen / Awad, Ola / Park, Tea Soon / Zambidis, Elias T / Feldman, Ricardo A

Stem cells translational medicine

2021 Volume 10, Issue 7, Page(s) 1081–1094

Abstract: Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in GBA1, the gene that encodes lysosomal β-glucocerebrosidase (GCase). Mild mutations in GBA1 cause type 1 non-neuronopathic GD, whereas severe mutations cause types 2 and 3 ... ...

Abstract	Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in GBA1, the gene that encodes lysosomal β-glucocerebrosidase (GCase). Mild mutations in GBA1 cause type 1 non-neuronopathic GD, whereas severe mutations cause types 2 and 3 neuronopathic GD (nGD). GCase deficiency results in the accumulation of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph). GlcSph is formed by deacylation of GlcCer by the lysosomal enzyme acid ceramidase. Brains from patients with nGD have high levels of GlcSph, a lipid believed to play an important role in nGD, but the mechanisms involved remain unclear. To identify these mechanisms, we used human induced pluripotent stem cell-derived neurons from nGD patients. We found that elevated levels of GlcSph activate mammalian target of rapamycin (mTOR) complex 1 (mTORC1), interfering with lysosomal biogenesis and autophagy, which were restored by incubation of nGD neurons with mTOR inhibitors. We also found that inhibition of acid ceramidase prevented both, mTOR hyperactivity and lysosomal dysfunction, suggesting that these alterations were caused by GlcSph accumulation in the mutant neurons. To directly determine whether GlcSph can cause mTOR hyperactivation, we incubated wild-type neurons with exogenous GlcSph. Remarkably, GlcSph treatment recapitulated the mTOR hyperactivation and lysosomal abnormalities in mutant neurons, which were prevented by coincubation of GlcSph with mTOR inhibitors. We conclude that elevated GlcSph activates an mTORC1-dependent pathogenic mechanism that is responsible for the lysosomal abnormalities of nGD neurons. We also identify acid ceramidase as essential to the pathogenesis of nGD, providing a new therapeutic target for treating GBA1-associated neurodegeneration.
MeSH term(s)	Acid Ceramidase/antagonists & inhibitors ; Gaucher Disease/drug therapy ; Gaucher Disease/genetics ; Humans ; Induced Pluripotent Stem Cells/cytology ; Lysosomes ; MTOR Inhibitors ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Neurons/cytology ; Psychosine/analogs & derivatives ; Psychosine/blood
Chemical Substances	MTOR Inhibitors ; Psychosine (2238-90-6) ; sphingosyl beta-glucoside (52050-17-6) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Acid Ceramidase (EC 3.5.1.23)
Language	English
Publishing date	2021-03-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6580
ISSN (online)	2157-6580
ISSN	2157-6580
DOI	10.1002/sctm.20-0386
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Article: Chemical reversion of conventional human pluripotent stem cells to a naïve-like state with improved multilineage differentiation potency

Park, Tea Soon / Zimmerlin, Ludovic / Evans-Moses, Rebecca / Zambidis, Elias T

Journal of visualized experiments. 2018 June 10, , no. 136

2018

Abstract	Naïve human pluripotent stem cells (N-hPSC) with improved functionality may have a wide impact in regenerative medicine. The goal of this protocol is to efficiently revert lineage-primed, conventional human pluripotent stem cells (hPSC) maintained on either feeder-free or feeder-dependent conditions to a naïve-like pluripotency with improved functionality. This chemical naïve reversion method employs the classical leukemia inhibitory factor (LIF), GSK3β, and MEK/ERK inhibition cocktail (LIF-2i), supplemented with only a tankyrase inhibitor XAV939 (LIF-3i). LIF-3i reverts conventional hPSC to a stable pluripotent state adopting biochemical, transcriptional, and epigenetic features of the human pre-implantation epiblast. This LIF-3i method requires minimal cell culture manipulation and is highly reproducible in a broad repertoire of human embryonic stem cell (hESC) and transgene-free human induced pluripotent stem cell (hiPSC) lines. The LIF-3i method does not require a re-priming step prior to the differentiation; N-hPSC can be differentiated directly with extremely high efficiencies and maintain karyotypic and epigenomic stabilities (including at imprinted loci). To increase the universality of the method, conventional hPSC are first cultured in the LIF-3i cocktail supplemented with two additional small molecules that potentiate protein kinase A (forskolin) and sonic hedgehog (sHH) (purmorphamine) signaling (LIF-5i). This brief LIF-5i adaptation step significantly enhances the initial clonal expansion of conventional hPSC and permits them to be subsequently naïve-reverted with LIF-3i alone in bulk quantities, thus obviating the need for picking/subcloning rare N-hPSC colonies later. LIF-5i-stabilized hPSCs are subsequently maintained in LIF-3i alone without the need of anti-apoptotic molecules. Most importantly, LIF-3i reversion markedly improves the functional pluripotency of a broad repertoire of conventional hPSC by decreasing their lineage-primed gene expression and erasing the interline variability of directed differentiation commonly observed amongst independent hPSC lines. Representative characterizations of LIF-3i-reverted N-hPSC are provided, and experimental strategies for functional comparisons of isogenic hPSC in lineage-primed vs. naïve-like states are outlined.
Keywords	NAD ADP-ribosyltransferase ; cAMP-dependent protein kinase ; cell culture ; cell differentiation ; embryonic germ layers ; embryonic stem cells ; enzyme inhibitors ; epigenetics ; forskolin ; gene expression ; humans ; leukemia inhibitory factor ; loci ; medicine ; mitogen-activated protein kinase ; tau-protein kinase ; transcription (genetics)
Language	English
Dates of publication	2018-0610
Size	p. e57921.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/57921
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Article ; Online: A role for the renin-angiotensin system in hematopoiesis.

Park, Tea Soon / Zambidis, Elias T

Haematologica

2009 Volume 94, Issue 6, Page(s) 745–747

MeSH term(s)	Angiotensin I/administration & dosage ; Angiotensin I/pharmacology ; Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/metabolism ; Cells, Cultured ; Cord Blood Stem Cell Transplantation/methods ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/metabolism ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Mice ; Peptide Fragments/administration & dosage ; Peptide Fragments/pharmacology ; Renin-Angiotensin System/physiology ; Transplantation, Heterologous
Chemical Substances	Peptide Fragments ; Angiotensin I (9041-90-1) ; angiotensin I (1-7) (IJ3FUK8MOF)
Language	English
Publishing date	2009-05-29
Publishing country	Italy
Document type	Editorial ; Comment
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2009.006965
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Article ; Online: Efficient and simultaneous generation of hematopoietic and vascular progenitors from human induced pluripotent stem cells.

Park, Tea Soon / Zimmerlin, Ludovic / Zambidis, Elias T

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2012 Volume 83, Issue 1, Page(s) 114–126

Abstract: The hematopoietic and vascular lineages are intimately entwined as they arise together from bipotent hemangioblasts and hemogenic endothelial precursors during human embryonic development. In vitro differentiation of human pluripotent stem cells toward ... ...

Abstract	The hematopoietic and vascular lineages are intimately entwined as they arise together from bipotent hemangioblasts and hemogenic endothelial precursors during human embryonic development. In vitro differentiation of human pluripotent stem cells toward these lineages provides opportunities for elucidating the mechanisms of hematopoietic genesis. We previously demonstrated the stepwise in vitro differentiation of human embryonic stem cells (hESC) to definitive erythromyelopoiesis through clonogenic bipotent primitive hemangioblasts. This system recapitulates an orderly hematopoiesis similar to human yolk sac development via the generation of mesodermal-hematoendothelial progenitor cells that give rise to endothelium followed by embryonic primitive and definitive hematopoietic cells. Here, we report that under modified feeder-free endothelial culture conditions, multipotent CD34⁺ CD45⁺ hematopoietic progenitors arise in mass quantities from differentiated hESC and human induced pluripotent stem cells (hiPSC). These hematopoietic progenitors arose directly from adherent endothelial/stromal cell layers in a manner resembling in vivo hematopoiesis from embryonic hemogenic endothelium. Although fibroblast-derived hiPSC lines were previously found inefficient in hemato-endothelial differentiation capacity, our culture system also supported robust hiPSC hemato-vascular differentiation at levels comparable to hESC. We present comparative differentiation results for simultaneously generating hematopoietic and vascular progenitors from both hESC and fibroblast-hiPSC. This defined, optimized, and low-density differentiation system will be ideal for direct single-cell time course studies of the earliest hematopoietic events using time-lapse videography, or bulk kinetics using flow cytometry analyses on emerging hematopoietic progenitors.
MeSH term(s)	Antigens, CD34/metabolism ; Blood Vessels/cytology ; Blood Vessels/physiology ; Cell Differentiation/physiology ; Cells, Cultured ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/physiology ; Flow Cytometry ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/immunology ; Hematopoietic Stem Cells/physiology ; Humans ; In Vitro Techniques ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/physiology ; Leukocyte Common Antigens/metabolism ; Stem Cells/cytology ; Stem Cells/immunology ; Stem Cells/physiology ; Time-Lapse Imaging
Chemical Substances	Antigens, CD34 ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2012-06-26
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.22090
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Article ; Online: Vascular progenitors generated from tankyrase inhibitor-regulated naïve diabetic human iPSC potentiate efficient revascularization of ischemic retina.

Park, Tea Soon / Zimmerlin, Ludovic / Evans-Moses, Rebecca / Thomas, Justin / Huo, Jeffrey S / Kanherkar, Riya / He, Alice / Ruzgar, Nensi / Grebe, Rhonda / Bhutto, Imran / Barbato, Michael / Koldobskiy, Michael A / Lutty, Gerard / Zambidis, Elias T

Nature communications

2020 Volume 11, Issue 1, Page(s) 1195

Abstract: Here, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated human ... ...

Abstract	Here, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated human naïve epiblast-like pluripotent state. Naïve diabetic vascular progenitors (N-DVP) differentiated from patient-specific naïve diabetic hiPSC (N-DhiPSC) possessed higher vascular functionality, maintained greater genomic stability, harbored decreased lineage-primed gene expression, and were more efficient in migrating to and re-vascularizing the deep neural layers of the ischemic retina than isogenic diabetic vascular progenitors (DVP). These findings suggest that reprogramming to a stable naïve human pluripotent stem cell state may effectively erase dysfunctional epigenetic donor cell memory or disease-associated aberrations in patient-specific hiPSC. More broadly, tankyrase inhibitor-regulated naïve hiPSC (N-hiPSC) represent a class of human stem cells with high epigenetic plasticity, improved multi-lineage functionality, and potentially high impact for regenerative medicine.
MeSH term(s)	Adult ; Animals ; Blood Vessels/pathology ; Cell Differentiation/drug effects ; Cell Line ; Cell Lineage/drug effects ; Cell Movement/drug effects ; Cellular Senescence/drug effects ; DNA Damage ; Diabetes Mellitus/pathology ; Enzyme Inhibitors/pharmacology ; Epigenesis, Genetic/drug effects ; Fibroblasts/drug effects ; Fibroblasts/pathology ; Histone Code ; Humans ; Induced Pluripotent Stem Cells/drug effects ; Induced Pluripotent Stem Cells/pathology ; Ischemia/pathology ; Ischemia/therapy ; Mice ; Organoids/drug effects ; Organoids/pathology ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Promoter Regions, Genetic/genetics ; Retina/pathology ; Stem Cells/drug effects ; Stem Cells/pathology ; Stem Cells/ultrastructure ; Tankyrases/antagonists & inhibitors ; Tankyrases/metabolism ; Teratoma/pathology ; Transcription, Genetic/drug effects
Chemical Substances	Enzyme Inhibitors ; Poly(ADP-ribose) Polymerase Inhibitors ; Tankyrases (EC 2.4.2.30)
Language	English
Publishing date	2020-03-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-14764-5
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