Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes

Terami, H.; Hidaka, Kumi; Katsumata, Takashi; Iio, Akio; Morisaki, Takayuki

doi:10.1016/j.bbrc.2004.10.103

Cited by 120 publications

(95 citation statements)

References 34 publications

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“…To characterize the factors that influence EB-size dependent differentiation into cardiac and endothelial cells, we evaluated the gene and protein expression of various extracellular matrix (ECM) molecules and soluble factors. Specifically, the basement membrane components that can be generated by endoderm within EBs (28) and WNT signaling family, which is known to be important in cardiogenesis and endothelial cell differentiation (4,26,29,30) were evaluated.…”

Section: Resultsmentioning

confidence: 99%

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Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11

Hwang

Chung

Ortmann

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

357

359

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Recently, various approaches for controlling the embryonic stem (ES) cell microenvironment have been developed for regulating cellular fate decisions. It has been reported that the lineage specific differentiation could be affected by the size of ES cell colonies and embryoid bodies (EBs). However, much of the underlying biology has not been well elucidated. In this study, we used microengineered hydrogel microwells to direct ES cell differentiation and determined the role of WNT signaling pathway in directing the differentiation. This was accomplished by forming ES cell aggregates within microwells to form different size EBs. We determined that cardiogenesis was enhanced in larger EBs (450 m in diameter), and in contrast, endothelial cell differentiation was increased in smaller EBs (150 m in diameter). Furthermore, we demonstrated that the EB-size mediated differentiation was driven by differential expression of WNTs, particularly noncanonical WNT pathway, according to EB size. The higher expression of WNT5a in smaller EBs enhanced endothelial cell differentiation. In contrast, the increased expression of WNT11 enhanced cardiogenesis. This was further validated by WNT5a-siRNA transfection assay and the addition of recombinant WNT5a. Our data suggest that EB size could be an important parameter in ES cell fate specification via differential gene expression of members of the noncanonical WNT pathway. Given the size-dependent response of EBs to differentiate to endothelial and cardiac lineages, hydrogel microwell arrays could be useful for directing stem cell fates and studying ES cell differentiation in a controlled manner.hydrogel microwells ͉ stem cell differentiation ͉ WNT signal pathway T he developmental versatility of embryonic stem (ES) cells offers a powerful approach for directing cell fate and is a promising source of progenitors for cell replacement therapy and tissue regeneration (1). ES cells can differentiate into a wide spectrum of cell types, such as cardiomyocytes and endothelial cells, by forming embryoid bodies (EBs) (2). Those lineages arise from distinct mesoderm subpopulations that develop sequentially from premesoderm cells (3). Such lineage specification is highly coordinated with differential changes in gene expression (4-8).Despite the therapeutic potential of ES cells, one of the significant challenges to their widespread clinical use, is the inability to homogeneously direct ES cell differentiation into specific lineages. One reason for the heterogeneity in EB differentiation is caused from variations in EB size (9, 10). To address this challenge for controlling the differentiation of ES cells, various microscale technologies (i.e., surface patterning, hydrogel microwells, and microfluidic systems) have been developed for directing the stem cell fate (11-15). Micropatterning techniques have been used to evaluate the effect of EB size on ES cell differentiation. For instance, microfabricated adhesive stencils were used to pattern ES cells for controlling initial ES cell aggregate sizes...

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Section: Resultsmentioning

confidence: 99%

“…Those lineages arise from distinct mesoderm subpopulations that develop sequentially from premesoderm cells (3). Such lineage specification is highly coordinated with differential changes in gene expression (4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11

Hwang

Chung

Ortmann

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

357

359

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“…Wnt-11, a noncanonical Wnt, promotes stem cell differentiation in several contexts [160]. For example, it induces hES cell exit from the pluripotent state, mesodermal/hematopoietic cell fate [161] and cardiac differentiation of mES cells [162]. In human embryonal carcinoma cells, Wnt-11 maintains neural progenitor cell proliferation but prevents further differentiation, which instead is driven by another noncanonical Wnt, Wnt-4 [68].…”

Section: Human Neural Stem and Progenitor Cells: Wnt Ligands And Recementioning

confidence: 99%

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

Bengoa-Vergniory

Kypta

2015

Cell. Mol. Life Sci.

136

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“…The cardiogenesis-promoting activity of GATA factors (Latinkic et al, 2003;Afouda et al, 2008) is shared by Wnt11b (Eisenberg and Eisenberg, 1999;Pandur et al, 2002;Terami et al, 2004). We, therefore, investigated whether Wnt11b could rescue the effect of depletion of individual GATAs on cardiogenesis.…”

Section: Wnt11b Differentially Mediates Function Of Gata Factors Durimentioning

confidence: 99%

Different requirements for GATA factors in cardiogenesis are mediated by non‐canonical Wnt signaling

Afouda¹,

Hoppler²

2011

Developmental Dynamics

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GATA factors and Wnt signals are key regulators of vertebrate cardiogenesis, but specific roles for individual GATA factors and how they interact with Wnt signaling remain unknown. We use loss of function and overexpression approaches to elucidate how these molecules regulate early cardiogenesis in Xenopus. In order to minimize indirect effects due to abnormal early embryogenesis, we use pluripotent embryonic tissues as cardiogenic assays. We confirm central roles for GATA4, 5, and 6 in cardiogenesis, but also discover individual and different requirements. We show that GATA4 or 6 regulate both cardiogenic potential and subsequent cardiomyocyte differentiation but that GATA5 is involved in regulating cardiomyocyte differentiation. We also show that Wnt11b signaling can rescue reduced cardiac differentiation resulting from loss of function of GATA4 and 6 but not GATA5. We conclude that Wnt11b mediates the differential requirements for GATA factors during vertebrate cardiogenesis. Developmental Dynamics 240:649-662,

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Wnt11 facilitates embryonic stem cell differentiation to Nkx2.5-positive cardiomyocytes

Cited by 120 publications

References 34 publications

Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11

Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11

Canonical and noncanonical Wnt signaling in neural stem/progenitor cells

Different requirements for GATA factors in cardiogenesis are mediated by non‐canonical Wnt signaling

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