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How a protein regulates blood cell fate

Zebrafish embryos

Image by Ian Johnston

Results of preclinical research explain the role endoglin plays in hematopoietic cell fate during embryogenesis.

Previous research showed that endoglin, a cell surface protein belonging to the TGF-beta receptor complex, is required for early hematopoietic lineage specification.

A new study shows that endoglin modulates the BMP and Wnt signaling pathways to encourage progenitor cells to develop into blood cells rather than cardiac cells.

This study was published in Nature Communications.

“During the early stages of development, cells have to make decisions very quickly,” said study author Rita Perlingeiro, PhD, of the University of Minnesota in Minneapolis.

“Fine-tuning of these early cell fate decisions can be easily disrupted by levels of key proteins within these cells. When one cell type is favored, this implies less of another. In this case, high levels of endoglin expression enhance the cell differentiation into blood cells, whereas cardiac cells are in deficit.”

Dr Perlingeiro and her colleagues made this discovery studying zebrafish and mouse models. The team wanted to pinpoint the mechanism underlying the dual function of endoglin in blood cell and cardiac cell fate.

The researchers found that endoglin is expressed in early mesoderm, and it marks both hematopoietic and cardiac progenitors.

Experiments showed that high levels of endoglin increase hematopoiesis while inhibiting cardiogenesis. And the levels of endoglin determine the activation of the BMP and Wnt signaling pathways.

With further investigation, the researchers identified JDP2, a member of the AP-1 transcription factor family, as an endoglin-dependent downstream target of Wnt signaling.

The team found that JDP2 expression is sufficient to establish blood cell fate when BMP and Wnt crosstalk is disturbed.

“The blood and heart systems are the first organs to develop in mammals, but the mechanisms regulating these earliest cell fate decisions are poorly understood,” Dr Perlingeiro said.

“By using multiple model systems, combined with specialized cell sorting technology and sequencing tools, our findings help uncover mechanisms previously unseen in the few cells engaged in these early development decisions.”

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Zebrafish embryos

Image by Ian Johnston

Results of preclinical research explain the role endoglin plays in hematopoietic cell fate during embryogenesis.

Previous research showed that endoglin, a cell surface protein belonging to the TGF-beta receptor complex, is required for early hematopoietic lineage specification.

A new study shows that endoglin modulates the BMP and Wnt signaling pathways to encourage progenitor cells to develop into blood cells rather than cardiac cells.

This study was published in Nature Communications.

“During the early stages of development, cells have to make decisions very quickly,” said study author Rita Perlingeiro, PhD, of the University of Minnesota in Minneapolis.

“Fine-tuning of these early cell fate decisions can be easily disrupted by levels of key proteins within these cells. When one cell type is favored, this implies less of another. In this case, high levels of endoglin expression enhance the cell differentiation into blood cells, whereas cardiac cells are in deficit.”

Dr Perlingeiro and her colleagues made this discovery studying zebrafish and mouse models. The team wanted to pinpoint the mechanism underlying the dual function of endoglin in blood cell and cardiac cell fate.

The researchers found that endoglin is expressed in early mesoderm, and it marks both hematopoietic and cardiac progenitors.

Experiments showed that high levels of endoglin increase hematopoiesis while inhibiting cardiogenesis. And the levels of endoglin determine the activation of the BMP and Wnt signaling pathways.

With further investigation, the researchers identified JDP2, a member of the AP-1 transcription factor family, as an endoglin-dependent downstream target of Wnt signaling.

The team found that JDP2 expression is sufficient to establish blood cell fate when BMP and Wnt crosstalk is disturbed.

“The blood and heart systems are the first organs to develop in mammals, but the mechanisms regulating these earliest cell fate decisions are poorly understood,” Dr Perlingeiro said.

“By using multiple model systems, combined with specialized cell sorting technology and sequencing tools, our findings help uncover mechanisms previously unseen in the few cells engaged in these early development decisions.”

Zebrafish embryos

Image by Ian Johnston

Results of preclinical research explain the role endoglin plays in hematopoietic cell fate during embryogenesis.

Previous research showed that endoglin, a cell surface protein belonging to the TGF-beta receptor complex, is required for early hematopoietic lineage specification.

A new study shows that endoglin modulates the BMP and Wnt signaling pathways to encourage progenitor cells to develop into blood cells rather than cardiac cells.

This study was published in Nature Communications.

“During the early stages of development, cells have to make decisions very quickly,” said study author Rita Perlingeiro, PhD, of the University of Minnesota in Minneapolis.

“Fine-tuning of these early cell fate decisions can be easily disrupted by levels of key proteins within these cells. When one cell type is favored, this implies less of another. In this case, high levels of endoglin expression enhance the cell differentiation into blood cells, whereas cardiac cells are in deficit.”

Dr Perlingeiro and her colleagues made this discovery studying zebrafish and mouse models. The team wanted to pinpoint the mechanism underlying the dual function of endoglin in blood cell and cardiac cell fate.

The researchers found that endoglin is expressed in early mesoderm, and it marks both hematopoietic and cardiac progenitors.

Experiments showed that high levels of endoglin increase hematopoiesis while inhibiting cardiogenesis. And the levels of endoglin determine the activation of the BMP and Wnt signaling pathways.

With further investigation, the researchers identified JDP2, a member of the AP-1 transcription factor family, as an endoglin-dependent downstream target of Wnt signaling.

The team found that JDP2 expression is sufficient to establish blood cell fate when BMP and Wnt crosstalk is disturbed.

“The blood and heart systems are the first organs to develop in mammals, but the mechanisms regulating these earliest cell fate decisions are poorly understood,” Dr Perlingeiro said.

“By using multiple model systems, combined with specialized cell sorting technology and sequencing tools, our findings help uncover mechanisms previously unseen in the few cells engaged in these early development decisions.”

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