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Article ; Online: Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Cells.

Gu, Mingxia

2018 Volume 98, Issue 1, Page(s) e64

Abstract: Endothelial cells (ECs) line the interior surface of blood and lymphatic vessels, and play a key role in a variety of physiological or pathological processes such as thrombosis, inflammation, or vascular wall remodeling. Human-induced pluripotent stem ... ...

Abstract	Endothelial cells (ECs) line the interior surface of blood and lymphatic vessels, and play a key role in a variety of physiological or pathological processes such as thrombosis, inflammation, or vascular wall remodeling. Human-induced pluripotent stem cell (iPSCs)-derived ECs provide a new opportunity for vascular regeneration and serve as a model to study the mechanism and to screen for novel therapies. We use developmental cues in a monolayer differentiation approach to efficiently generate mesoderm cells from iPSCs via small-molecule activation of WNT signaling in chemically defined medium for 4 days, and subsequent EC specification using vascular endothelial growth factor and fibroblast growth factor for another 4 days. After 8 days of differentiation, mature ECs are further purified using magnetic-activated cell sorting for the EC surface marker CD144. These ECs exhibit molecular and cellular characteristics consistent with native ECs, such as expression of specific surface markers, formation of tube-like structures and acetylated low-density lipoprotein uptake. © 2018 by John Wiley & Sons, Inc.
Language	English
Publishing date	2018-07-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2179054-1
ISSN	1934-8258 ; 1934-8266
ISSN (online)	1934-8258
ISSN	1934-8266
DOI	10.1002/cphg.64
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Article ; Online: Unlocking the potential of induced pluripotent stem cells for neonatal disease modeling and drug development.

Liu, Ziyi / Lami, Bonny / Ikonomou, Laertis / Gu, Mingxia

Seminars in perinatology

2023 Volume 47, Issue 3, Page(s) 151729

Abstract: Neonatal lung and heart diseases, albeit rare, can result in poor quality of life, often require long-term management and/or organ transplantation. For example, Congenital Heart Disease (CHD) is one of the most common type of congenital disabilities, ... ...

Abstract	Neonatal lung and heart diseases, albeit rare, can result in poor quality of life, often require long-term management and/or organ transplantation. For example, Congenital Heart Disease (CHD) is one of the most common type of congenital disabilities, affecting nearly 1% of the newborns, and has complex and multifactorial causes, including genetic predisposition and environmental influences. To develop new strategies for heart and lung regeneration in CHD and neonatal lung disease, human induced pluripotent stem cells (hiPSCs) provide a unique and personalized platform for future cell replacement therapy and high-throughput drug screening. Additionally, given the differentiation potential of iPSCs, cardiac cell types such as cardiomyocytes, endothelial cells, and fibroblasts and lung cell types such Type II alveolar epithelial cells can be derived in a dish to study the fundamental pathology during disease progression. In this review, we discuss the applications of hiPSCs in understanding the molecular mechanisms and cellular phenotypes of CHD (e.g., structural heart defect, congenital valve disease, and congenital channelopathies) and congenital lung diseases, such as surfactant deficiencies and Brain-Lung-Thyroid syndrome. We also provide future directions for generating mature cell types from iPSCs, and more complex hiPSC-based systems using three-dimensional (3D) organoids and tissue-engineering. With these potential advancements, the promise that hiPSCs will deliver new CHD and neonatal lung disease treatments may soon be fulfilled.
MeSH term(s)	Infant, Newborn ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Endothelial Cells ; Quality of Life ; Heart Defects, Congenital/therapy ; Drug Development ; Lung Diseases/therapy ; Lung Diseases/metabolism ; Infant, Newborn, Diseases
Language	English
Publishing date	2023-03-11
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	752403-1
ISSN	1558-075X ; 0146-0005
ISSN (online)	1558-075X
ISSN	0146-0005
DOI	10.1016/j.semperi.2023.151729
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Zs.A 1339: Show issues

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Article ; Online: Follow your heart and trust your gut: Co-development of heart and gut tissue in organoids.

Gu, Mingxia / Zorn, Aaron M

Cell stem cell

2021 Volume 28, Issue 12, Page(s) 2037–2038

Abstract: Organogenesis is orchestrated by the interaction of different embryonic tissues. Recent reports in Cell Stem Cell (Silva et al., 2021; Rossi et al., 2021) and Nature Biotechnology (Drakhlis et al., 2021) recapitulate the co-development of embryonic ... ...

Abstract	Organogenesis is orchestrated by the interaction of different embryonic tissues. Recent reports in Cell Stem Cell (Silva et al., 2021; Rossi et al., 2021) and Nature Biotechnology (Drakhlis et al., 2021) recapitulate the co-development of embryonic mesoderm and endoderm in PSCs to promote formation of complex heart and gut organoids.
MeSH term(s)	Endoderm ; Heart ; Mesoderm ; Organogenesis ; Organoids
Language	English
Publishing date	2021-12-10
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2021.09.003
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Zs.A 6589: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Growing With the Flow: Insights Into How Flow Mediates Endocardial Fibroelastosis.

Pek, Nicole Min Qian / Gu, Mingxia

JACC. Basic to translational science

2021 Volume 6, Issue 12, Page(s) 1000–1002

Language	English
Publishing date	2021-12-27
Publishing country	United States
Document type	Editorial
ISSN	2452-302X
ISSN (online)	2452-302X
DOI	10.1016/j.jacbts.2021.09.007
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Article ; Online: Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders.

Chang, Xuyao / Gu, Mingxia / Tchieu, Jason

Cells

2022 Volume 11, Issue 3

Abstract: Advances in human pluripotent stem cell (hPSC) technology allow one to deconstruct the human body into specific disease-relevant cell types or create functional units representing various organs. hPSC-based models present a unique opportunity for the ... ...

Abstract	Advances in human pluripotent stem cell (hPSC) technology allow one to deconstruct the human body into specific disease-relevant cell types or create functional units representing various organs. hPSC-based models present a unique opportunity for the study of co-occurring disorders where "cause and effect" can be addressed. Poor neurodevelopmental outcomes have been reported in children with congenital heart diseases (CHD). Intuitively, abnormal cardiac function or surgical intervention may stunt the developing brain, leading to neurodevelopmental disorders (NDD). However, recent work has uncovered several genetic variants within genes associated with the development of both the heart and brain that could also explain this co-occurrence. Given the scalability of hPSCs, straightforward genetic modification, and established differentiation strategies, it is now possible to investigate both CHD and NDD as independent events. We will first overview the potential for shared genetics in both heart and brain development. We will then summarize methods to differentiate both cardiac & neural cells and organoids from hPSCs that represent the developmental process of the heart and forebrain. Finally, we will highlight strategies to rapidly screen several genetic variants together to uncover potential phenotypes and how therapeutic advances could be achieved by hPSC-based models.
MeSH term(s)	Cell Differentiation/genetics ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/metabolism ; Humans ; Neurodevelopmental Disorders/genetics ; Neurodevelopmental Disorders/metabolism ; Organoids/metabolism ; Pluripotent Stem Cells/metabolism
Language	English
Publishing date	2022-01-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11030460
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Article ; Online: Distributed consensus of discrete time-varying linear multi-agent systems with event-triggered intermittent control.

Gu, Mingxia / Yu, Zhiyong / Jiang, Haijun / Huang, Da

Mathematical biosciences and engineering : MBE

2022 Volume 21, Issue 1, Page(s) 415–443

Abstract: The consensus problem of discrete time-varying linear multi-agent systems (MASs) is studied in this paper. First, an event-triggered intermittent control (ETIC) protocol is designed, aided by a class of auxiliary functions. Under this protocol, some ... ...

Abstract	The consensus problem of discrete time-varying linear multi-agent systems (MASs) is studied in this paper. First, an event-triggered intermittent control (ETIC) protocol is designed, aided by a class of auxiliary functions. Under this protocol, some sufficient conditions for all agents to achieve consensus are established by constructing an error dynamical system and applying the Lyapunov function. Second, in order to further reduce the communication burden, an improved event triggered intermittent control (I-ETIC) strategy is presented, along with corresponding convergence analysis. Notably, the difference between the two control protocols lies in the fact that the former protocol only determines when to control or not based on the trigger conditions, while the latter, building upon this, designs new event trigger conditions for the update of the controller during the control stage. Finally, two numerical simulation examples are provided to demonstrate the effectiveness of the theoretical results.
Language	English
Publishing date	2022-12-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2265126-3
ISSN	1551-0018 ; 1551-0018
ISSN (online)	1551-0018
ISSN	1551-0018
DOI	10.3934/mbe.2024019
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Article ; Online: Delving into the Molecular World of Single Ventricle Congenital Heart Disease.

Yu, Zhiyun / Pek, Nicole Min Qian / Gu, Mingxia

Current cardiology reports

2022 Volume 24, Issue 5, Page(s) 463–471

Abstract: Purpose of review: Given a general lack of emphasis on the molecular underpinnings of single ventricle (SV) congenital heart diseases (CHD), our review highlights and summarizes recent advances in uncovering the genetic and molecular mechanisms in SV ... ...

Abstract	Purpose of review: Given a general lack of emphasis on the molecular underpinnings of single ventricle (SV) congenital heart diseases (CHD), our review highlights and summarizes recent advances in uncovering the genetic and molecular mechanisms in SV CHD etiology. Recent findings: While common SV-associated genetic mutations were found in key cardiac transcription factors, other mutations were sporadic. With advances in genetic sequencing technologies and animal models, more disease-associated factors have been identified to act in critical cardiac signaling pathways such as NOTCH, Wnt, and TGF signaling. Recent studies have also revealed that different cardiac lineages play different roles in disease pathogenesis. SV defects are attributed to complex combinations of genetic mutations, indicating that sophisticated spatiotemporal regulation of gene transcription networks and functional cellular pathways govern disease progression. Future studies will warrant in-depth investigations into better understanding how different genetic factors converge to influence common downstream cellular pathways, resulting in SV abnormalities.
MeSH term(s)	Heart Defects, Congenital/genetics ; Heart Ventricles/abnormalities ; Humans
Language	English
Publishing date	2022-02-26
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2055373-0
ISSN	1534-3170 ; 1523-3782
ISSN (online)	1534-3170
ISSN	1523-3782
DOI	10.1007/s11886-022-01667-8
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Zs.A 5524: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Endocardium in Hypoplastic Left Heart Syndrome: Implications from In Vitro Study.

Yu, Zhiyun / Liu, Ziyi / Ravichandran, Vidhya / Lami, Bonny / Gu, Mingxia

Journal of cardiovascular development and disease

2022 Volume 9, Issue 12

Abstract: Endocardium lines the inner layer of the heart ventricle and serves as the source of valve endothelial cells and interstitial cells. Previously, endocardium-associated abnormalities in hypoplastic left heart syndrome (HLHS) have been reported, including ... ...

Abstract	Endocardium lines the inner layer of the heart ventricle and serves as the source of valve endothelial cells and interstitial cells. Previously, endocardium-associated abnormalities in hypoplastic left heart syndrome (HLHS) have been reported, including endocardial fibroelastosis (EFE) and mitral and aortic valve malformation. However, few mechanistic studies have investigated the molecular pathological changes in endocardial cells. Recently, the emergence of a powerful in vitro system-induced pluripotent stem cells (iPSCs)-was applied to study various genetic diseases, including HLHS. This review summarized current in vitro studies in understanding the endocardial pathology in HLHS, emphasizing new findings of the cellular phenotypes and underlying molecular mechanisms. Lastly, a future perspective is provided regarding the better recapitulation of endocardial phenotypes in a dish.
Language	English
Publishing date	2022-12-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd9120442
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Article ; Online: Hypoplastic left heart syndrome (HLHS): molecular pathogenesis and emerging drug targets for cardiac repair and regeneration.

Bejjani, Anthony T / Wary, Neil / Gu, Mingxia

Expert opinion on therapeutic targets

2021 Volume 25, Issue 8, Page(s) 621–632

Abstract: Introduction: Hypoplastic left heart syndrome (HLHS) is a severe developmental defect characterized by the underdevelopment of the left ventricle along with aortic and valvular defects. Multiple palliative surgeries are required for survival. Emerging ... ...

Abstract	Introduction: Hypoplastic left heart syndrome (HLHS) is a severe developmental defect characterized by the underdevelopment of the left ventricle along with aortic and valvular defects. Multiple palliative surgeries are required for survival. Emerging studies have identified potential mechanisms for the disease onset, including genetic and hemodynamic causes. Genetic variants associated with HLHS include transcription factors, chromatin remodelers, structural proteins, and signaling proteins necessary for normal heart development. Nonetheless, current therapies are being tested clinically and have shown promising results at improving cardiac function in patients who have undergone palliative surgeries. Areas covered: We searched PubMed and clinicaltrials.gov to review most of the mechanistic research and clinical trials involving HLHS. This review discusses the anatomy and pathology of HLHS hearts. We highlight some of the identified genetic variants that underly the molecular pathogenesis of HLHS. Additionally, we discuss some of the emerging therapies and their limitations for HLHS. Expert opinion: While HLHS etiology is largely obscure, palliative therapies remain the most viable option for the patients. It is necessary to generate animal and stem cell models to understand the underlying genetic causes directly leading to HLHS and facilitate the use of gene-based therapies to improve cardiac development and regeneration.
MeSH term(s)	Animals ; Humans ; Hypoplastic Left Heart Syndrome/drug therapy ; Hypoplastic Left Heart Syndrome/genetics ; Regeneration/genetics ; Transcription Factors
Chemical Substances	Transcription Factors
Language	English
Publishing date	2021-09-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2021.1978069
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Zs.A 5244: Show issues

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Article ; Online: Isolation of Endocardial and Coronary Endothelial Cells from the Ventricular Free Wall of the Rat Heart.

Klein, Alyssa / Bayrau, Bethel / Miao, Yifei / Gu, Mingxia

Journal of visualized experiments : JoVE

2020 , Issue 158

Abstract: It has been shown that endocardial endothelial cells (EECs) and coronary endothelial cells (CECs) differ in origin, development, markers, and functions. Consequently, these two cell populations play unique roles in cardiac diseases. Current studies ... ...

Abstract	It has been shown that endocardial endothelial cells (EECs) and coronary endothelial cells (CECs) differ in origin, development, markers, and functions. Consequently, these two cell populations play unique roles in cardiac diseases. Current studies involving isolated endothelial cells investigate cell populations consisting of both EECs and CECs. This protocol outlines a method to independently isolate these two cell populations for cell-specific characterization. Following the collection of the left and right ventricular free wall, endothelial cells from the outer surface and inner surface are separately liberated using a digestion buffer solution. The sequential digestion of the outer surface and the inner endocardial layer retained separation of the two endothelial cell populations. The separate isolation of EECs and CECs is further verified through the identification of markers specific to each population. Based on previously published single cell RNA profiling in the mouse heart, the Npr3, Hapln1, and Cdh11 gene expression is unique to EECs; while Fabp4, Mgll, and Cd36 gene expression is unique to CECs. qPCR data revealed enriched expression of these characteristic markers in their respective samples, indicating successful EEC and CEC isolation, as well as maintenance of cell phenotype, enabling further cell-specific functional analysis.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Cells, Cultured ; Coronary Vessels/cytology ; Coronary Vessels/metabolism ; Endocardium/cytology ; Endocardium/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Gene Expression Profiling ; Heart/physiology ; Heart Ventricles/cytology ; Heart Ventricles/metabolism ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/61126
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