Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells

Wang, Lina; Su, Weijun; Du, Wei; Wang, Lijun; Han, Zhongchao; Zheng, Guoguang; Li, Zongjin

doi:10.1007/s12015-014-9582-4

Cited by 28 publications

(15 citation statements)

References 35 publications

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“…In addition, vascular invasion is an important step in metastasis to distant sites, and angiogenesis and its regulators are associated with tumor growth and prognosis in various solid tumors, including lung cancer [42, 43]. In this context, miR-27b-3p is a pro-angiogenic microRNA [40, 44] that is up-regulated in vascular endothelial cells [45–47]. In a recent mouse study, increased miR-27b-3p expression resulted in enhanced neovascularization and contributed to tumor growth [44].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status

et al. 2016

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Lung adenocarcinoma has distinctive clinicopathological features that are related to specific genetic alterations, including EGFR and KRAS mutations and ALK rearrangement. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate many important biological processes and influence cancer phenotypes. This study retrospectively investigated microRNA expression profiles, and their clinicopathological implications, in lung adenocarcinoma according to genetic status (EGFR, KRAS, ALK, and triple negative). A total of 72 surgically resected lung adenocarcinoma specimens (19 EGFR-mutated, 17 KRAS-mutated, 16 ALK-rearranged, and 20 triple negative cancers) were screened for 23 microRNAs using quantitative real-time reverse transcriptase polymerase chain reaction. We then evaluated the associations between the microRNA expressions and the cancers’ genetic and clinicopathological features. Eight microRNAs were associated with clinicopathological features, such as male sex and ever-smoker status (high miR-373-3p, miR-1343-3p, miR-138-1-3p, and miR-764; low miR-27b-3p) and vascular invasion (high miR-27b-3p; low miR-1343-3p and miR-764). Clustering and discriminant analyses revealed that the microRNA expression patterns in the ALK group were different from those in the EGFR and KRAS groups. Five microRNAs (high miR-1343-3p; low miR-671-3p, miR-103a-3p, let-7e, and miR-342-3p) were especially distinctive in the ALK group, compared to the EGFR and KRAS groups. Moreover, a significant association was observed between ALK-rearrangement, decreased miR-342-3p expression, and immunohistochemical loss of E-cadherin. Therefore, microRNA expression profiles appear to have distinctive clinicopathological implications in ALK-rearranged lung adenocarcinoma. Furthermore, the association of ALK rearrangement, decreased miR-342-3p expression, and E-cadherin loss might indicate that miR-342-3p is involved in the ALK-associated phenotypes and epithelial-mesenchymal transition.

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Section: Discussionmentioning

confidence: 99%

MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status

et al. 2016

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“…Yoo et al, [88] reported two novel miRs, miR-6086 and miR-6087, which target vascular endothelial (VE-)cadherin and endoglin, respectively, and their expression is down regulated during EC differentiation [88]. Another study demonstrated that the expression of miR-99b, miR-181a, and miR-181b was increased in ECs during differentiation [89], which was reconfirmed by another group recently [90]. Interestingly, although over expression of these miRs promotes EC differentiation, their knockdown has no significant impact on EC differentiation of hESCs [89].…”

Section: Esc Specific Mirs Regulating Their Commitment To Ecsmentioning

confidence: 73%

“…Recently, Chen and colleagues identified miR-199a and miR-199b as differentially regulated miRs during EC differentiation [109] [110] but their role in EC differentiation needs to be verified. Likewise, Wang et al, [90] have performed an extensive miR profiling of hiPSCs and differentiated ECs and identified several differentially regulated miRs including miR-20a, miR-20b, miR-27b, miR-100, miR-125a-5p, miR-137, miR-149, miR-181a, miR-210, miR-222, and miR-296-5p, however, their role in EC differentiation of iPSCs is not verified yet.…”

Section: Induced Pluripotent Sc-specific Mirsmentioning

confidence: 99%

MicroRNAs as Modulators of Endothelial Differentiation of Stem Cells

Gunduz¹,

Aslam²

2016

JBiSE

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MicroRNAs (miRs) are a class of small (~22 nucleotides), widely distributed, and highly conserved non-coding RNA molecules and play an important post-transcriptional regulatory role by targeting mRNA. Embryonic and induced pluripotent stem cells (ESCs and iPSC, respectively) hold great promise for vascular regenerative therapies. However, several limitations currently prohibit their therapeutic use. The importance of miRs in controlling the gene expression profile of a particular cell type is emerging and a multitude of miRs have been identified that play key roles in vascular development and regeneration. A combination of pluripotency transcription factors and different miRs not only enhances the pluripotency of stem cells but also has been reported to enhance their endothelial differentiation. This review will summarize the findings that focus different miR clusters in the induction, maintenance, and directed endothelial differentiation of ESCs and iPSCs.

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“…Generation of endothelial cells from pluripotent stem cells of various origins has been reported and is now well established . Characterization of the generated endothelial cells, including gene expression pattern, has revealed significant information regarding overall expression profile of endothelial specific genes . These studies have also lead to significant insights into the vascular bed/organ‐specific characteristics of endothelial cells, as well as contributions of signaling pathways, epigenetics regulators, secreted molecules, and membrane bound cell surface receptors in regulation of endothelial‐specific gene expression .…”

Section: Introductionmentioning

confidence: 99%

Regulation of von Willebrand Factor Gene in Endothelial Cells That Are Programmed to Pluripotency and Differentiated Back to Endothelial Cells

et al. 2019

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Endothelial cells play a central role in physiological function and pathophysiology of blood vessels in health and disease. However, the molecular mechanism that establishes the endothelial phenotype, and contributes to its signature cell type-specific gene expression, is not yet understood. We studied the regulation of a highly endothelial-specific gene, von Willebrand factor (VWF), in induced pluripotent stem cells generated from primary endothelial cells (human umbilical vein endothelial cells [HUVEC] into a pluripotent state [HiPS]) and subsequently differentiated back into endothelial cells. This allowed us to explore how VWF expression is regulated when the endothelial phenotype is revoked (endothelial cells to HiPS), and re-established (HiPS back to endothelial cells [EC-Diff]). HiPS were generated from HUVECs, their pluripotency established, and then differentiated back to endothelial cells. We established phenotypic characteristics and robust angiogenic function of EC-Diff. Gene array analyses, VWF chromatin modifications, and transacting factors binding assays were performed on the three cell types (HUVEC, HiPS, and EC-Diff). The results demonstrated that generally cohorts of transacting factors that function as transcriptional activators, and those that contribute to histone acetylation and DNA demethylation, were significantly decreased in HiPS compared with HUVECs and EC-Diff. In contrast, there were significant increases in the gene expression levels of epigenetic modifiers that function as methyl transferases in HiPS compared with endothelial cells. The results demonstrated that alterations in chromatin modifications of the VWF gene, in addition to expression and binding of transacting factors that specifically function as activators, are responsible for establishing endothelial specific regulation of the VWF gene. STEM CELLS 2019;37:542-554 SIGNIFICANCE STATEMENTIn these studies, a novel approach involving generation and differentiation of induced pluripotent stem cells is used to revoke and subsequently re-establish a specific cell phenotype, namely endothelial cells, to explore transcriptional regulatory networks that are associated with establishing cell type specific gene regulation. It provides a novel approach, compared with classic analyses of differential gene regulation among cells of distinct phenotypes, toward determining how cell type specific gene expression is regulated. The process allows for determining simultaneously what the critical components that contribute to silencing are, as well as activating target cell-type specific gene regulation.

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Gene and MicroRNA Profiling of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells

Abstract: hiPSC-ECs and hESC-ECs exhibited a high degree of similarity with HUVECs in EC-associated genes expression. And the miRNA profiling analysis revealed significant differences between hiPSCs and hESCs, but a high degree of similarity between hiPSC-ECs and hESC-ECs.

Cited by 28 publications

References 35 publications

MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status

MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status

MicroRNAs as Modulators of Endothelial Differentiation of Stem Cells

Regulation of von Willebrand Factor Gene in Endothelial Cells That Are Programmed to Pluripotency and Differentiated Back to Endothelial Cells

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