Gender-specific characteristics of hypertrophic response in cardiomyocytes derived from human embryonic stem cells

Introduction: Gender-specific phenotypes of the heart were reported with respect to both physiology and pathology. While most differences were associated with the sex hormones, differential expression of genes received special attention, particularly X-Y chromosomes’ genes. Methods: Here, we compared cardiogenesis by gene expression analysis of lineage specific markers and X-Y chromosomes’ genes, during in vitro differentiation of XY and XX human embryonic stem cells (hESC), in a hormone-free setup. Results: Downregulation of pluripotency marker (NANOG) and upregulation of cardiac mesoderm and progenitor markers (GATA4, TBX5, NKX2.5, ISL1) was remained temporally similar in differentiating XY and XX hESCs. Isoproterenol treatment of XY and XX hESC-derived cardiomyocytes (hESCCM) induced hypertrophy in a sex-specific manner, with female cardiomyocytes showing response at higher isoproterenol concentration and a later time point of differentiation. Interestingly, KDM5C as an X-linked gene, was markedly upregulated in both hypertrophied male and female cardiomyocytes. Conclusion: Collectively, our results indicated a temporally identical cardiogenesis, but more susceptibility of XY hESC-CM to hypertrophic stimulus in a hormone-free condition.

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Faculty Opinions recommendation of INS(GFP/w) human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13984975.15442093 ◽

2012 ◽

Author(s):

Gordon Weir

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Insulin Producing Cells

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Faculty Opinions recommendation of CORTECON: a temporal transcriptome analysis of in vitro human cerebral cortex development from human embryonic stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718478232.793498745 ◽

2014 ◽

Author(s):

Vijay Tiwari ◽

Johannes Jung

Keyword(s):

Stem Cells ◽

Cerebral Cortex ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Transcriptome Analysis ◽

Embryonic Stem ◽

Human Cerebral Cortex ◽

Cerebral Cortex Development

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Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

Tissue Engineering and Regenerative Medicine ◽

10.1007/s13770-021-00359-8 ◽

2021 ◽

Author(s):

Eun-Young Shin ◽

Seah Park ◽

Won Yun Choi ◽

Dong Ryul Lee

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

Male Hypogonadism ◽

Testosterone Levels ◽

Sequence Of Events ◽

Short Period ◽

Molecular Compounds

Abstract Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

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Nanofiber-Based in Vitro System for High Myogenic Differentiation of Human Embryonic Stem Cells

Biomacromolecules ◽

10.1021/bm4009843 ◽

2013 ◽

Vol 14 (12) ◽

pp. 4207-4216 ◽

Cited By ~ 29

Author(s):

Matthew Leung ◽

Ashleigh Cooper ◽

Soumen Jana ◽

Ching-Ting Tsao ◽

Timothy A. Petrie ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Myogenic Differentiation ◽

Embryonic Stem ◽

In Vitro System

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Smooth-Muscle-Like Cells Derived from Human Embryonic Stem Cells Support and Augment Cord-Like Structures In Vitro

Stem Cell Reviews and Reports ◽

10.1007/s12015-010-9144-3 ◽

2010 ◽

Vol 6 (2) ◽

pp. 237-247 ◽

Cited By ~ 49

Author(s):

Elaine Vo ◽

Donny Hanjaya-Putra ◽

Yuanting Zha ◽

Sravanti Kusuma ◽

Sharon Gerecht

Keyword(s):

Stem Cells ◽

Smooth Muscle ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem

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Correlation of mesodermal and pluripotency gene expression during in vitro differentiation of human embryonic stem cells

Fertility and Sterility ◽

10.1016/j.fertnstert.2013.07.487 ◽

2013 ◽

Vol 100 (3) ◽

pp. S457

Author(s):

S.-Y. Ku ◽

Y.Y. Kim ◽

H. Kim ◽

S.H. Kim ◽

Y.M. Choi ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Embryonic Stem ◽

In Vitro Differentiation ◽

Pluripotency Gene

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Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions

Blood ◽

10.1182/blood-2010-07-295246 ◽

2011 ◽

Vol 117 (11) ◽

pp. 3065-3075 ◽

Cited By ~ 36

Author(s):

Olena Klimchenko ◽

Antonio Di Stefano ◽

Birgit Geoerger ◽

Sofiane Hamidi ◽

Paule Opolon ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Human Embryonic Stem Cells ◽

Fetal Liver ◽

Critical Role ◽

Embryonic Stem ◽

Blood Monocytes ◽

Monocytic Cell ◽

Monocytic Cells

Abstract The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14lowCD16− precursor to form CD14highCD16+ cells without producing the CD14highCD16− cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.

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