BMP4 initiates human embryonic stem cell differentiation to trophoblast

Xu, Ren‐He; Chen, Xin; Li, Dong S.; Li, Rui; Addicks, Gregory C.; Glennon, Clay; Zwaka, Thomas P.; Thomson, James A.

doi:10.1038/nbt761

Cited by 1,024 publications

(1,011 citation statements)

References 31 publications

Supporting

Mentioning

934

Contrasting

Unclassified

Order By: Relevance

“…Dkk1, a potent inducer of heart development [3,10,11], synergises with BMP antagonism to specify heart tissue in non-cardiogenic mesoderm from Xenopus embryos [12]. It has been shown that long-term treatment of hESCs with BMP4 induces trophoblast-like cell differentiation [13], while short-term treatment initiates mesoderm formation [14]. Together, these results suggest that inhibiting BMP signaling after mesoderm formation facilitates cardiac development.…”

Section: Introductionmentioning

confidence: 61%

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

et al. 2010

View full text Add to dashboard Cite

Although myocyte cell transplantation studies have suggested a promising therapeutic potential for myocardial infarction, a major obstacle to the development of clinical therapies for myocardial repair is the difficulties associated with obtaining relatively homogeneous ventricular myocytes for transplantation. Human embryonic stem cells (hESCs) are a promising source of cardiomyocytes. Here we report that retinoid signaling regulates the fate specification of atrial versus ventricular myocytes during cardiac differentiation of hESCs. We found that both Noggin and the panretinoic acid receptor antagonist BMS-189453 (RAi) significantly increased the cardiac differentiation efficiency of hESCs. To investigate retinoid functions, we compared Noggin+RAi-treated cultures with Noggin+RA-treated cultures. Our results showed that the expression levels of the ventricular-specific gene IRX-4 were radically elevated in Noggin+RAi-treated cultures. MLC-2V, another ventricular-specific marker, was expressed in the majority of the cardiomyocytes in Noggin+RAi-treated cultures, but not in the cardiomyocytes of Noggin+RA-treated cultures. Flow cytometry analysis and electrophysiological studies indicated that with 64.7 ± 0.88% (mean ± s.e.m) cardiac differentiation efficiency, 83% of the cardiomyocytes in Noggin+RAi-treated cultures had embryonic ventricular-like action potentials (APs). With 50.7 ± 1.76% cardiac differentiation efficiency, 94% of the cardiomyocytes in Noggin+RA-treated cultures had embryonic atrial-like APs. These results were further confirmed by imaging studies that assessed the patterns and properties of the Ca 2+ sparks of the cardiomyocytes from the two cultures. These findings demonstrate that retinoid signaling specifies the atrial versus ventricular differentiation of hESCs. This study also shows that relatively homogeneous embryonic atrial-and ventricular-like myocyte populations can be efficiently derived from hESCs by specifically regulating Noggin and retinoid signals.

show abstract

Section: Introductionmentioning

confidence: 61%

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

et al. 2010

View full text Add to dashboard Cite

show abstract

“…2C; supplementary material Fig. S10A,B), indicative of mesoderm (Bernando et al, 2011) or trophectoderm (Xu et al, 2002) specification. Taken together these results suggest that this differentiation protocol generates primarily ectodermal cells, including epidermal keratinocyte progenitor cells.…”

Section: Research Articlementioning

confidence: 99%

Notch signaling represses p63 expression in the developing surface ectoderm

Tadeu

Horsley

2013

Development

View full text Add to dashboard Cite

MiceK14-H2BGFP transgenic mice (Tumbar et al., 2004) SUMMARYThe development of the mature epidermis requires a coordinated sequence of signaling events and transcriptional changes to specify surface ectodermal progenitor cells to the keratinocyte lineage. The initial events that specify epidermal keratinocytes from ectodermal progenitor cells are not well understood. Here, we use both developing mouse embryos and human embryonic stem cells (hESCs) to explore the mechanisms that direct keratinocyte fate from ectodermal progenitor cells. We show that both hESCs and murine embryos express p63 before keratin 14. Furthermore, we find that Notch signaling is activated before p63 expression in ectodermal progenitor cells. Inhibition of Notch signaling pharmacologically or genetically reveals a negative regulatory role for Notch signaling in p63 expression during ectodermal specification in hESCs or mouse embryos, respectively. Taken together, these data reveal a role for Notch signaling in the molecular control of ectodermal progenitor cell specification to the epidermal keratinocyte lineage.

show abstract

“…One reason of this delay is the huge difference between mouse and human in response to certain extracellular signals. BMP signaling, which maintains the pluripotency of mESCs, promote the hESC to differentiate, preferably into trophblast (Xu et al, 2002). In contrast, the FGF2, which is routinely used in hESC culture, initiate the differentiation of mESCs (Lanner and Rossant, 2010).…”

Section: Distinctive Neural Differentiation Of Human Pscsmentioning

confidence: 99%

Specification of functional neurons and glia from human pluripotent stem cells

Jiang

Zhang

2012

Protein Cell

View full text Add to dashboard Cite

Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise in regenerative medicine as they are an important source of functional cells for potential cell replacement. These human PSCs, similar to their counterparts of mouse, have the full potential to give rise to any type of cells in the body. However, for the promise to be fulfilled, it is necessary to convert these PSCs into functional specialized cells. Using the developmental principles of neural lineage specification, human ESCs and iPSCs have been effectively differentiated to regional and functional specific neurons and glia, such as striatal gama-aminobutyric acid (GABA)-ergic neurons, spinal motor neurons and myelin sheath forming oligodendrocytes. The human PSCs, in general differentiate after the similar developmental program as that of the mouse: they use the same set of cell signaling to tune the cell fate and they share a conserved transcriptional program that directs the cell fate transition. However, the human PSCs, unlike their counterparts of mouse, tend to respond divergently to the same set of extracellular signals at certain stages of differentiation, which will be a critical consideration to translate the animal model based studies to clinical application.

show abstract

BMP4 initiates human embryonic stem cell differentiation to trophoblast

Cited by 1,024 publications

References 31 publications

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

Direct differentiation of atrial and ventricular myocytes from human embryonic stem cells by alternating retinoid signals

Notch signaling represses p63 expression in the developing surface ectoderm

Specification of functional neurons and glia from human pluripotent stem cells

Contact Info

Product

Resources

About