Technology
Fri May 22, 2020 11:6
Epigenetic Mechanisms of Blood Cell Differentiation
TEHRAN (FNA)- On average, the human body contains 35 trillion red blood cells (RBCs). Approximately three million of these small disc-shaped cells die in one second. But in this second, the same number is also produced to maintain the level of active RBCs. Interestingly, all of these cells undergo a multi-level differentiation process called erythropoiesis. They start from hematopoietic stem cells (HSCs), the precursors to every blood cell including all types of immune cells, and differentiate then, firstly, into multipotent progenitor cells (MPPs) followed by a gradual process of specialization into mature red blood cells.

If this differentiation process fails, it can be detrimental to our health. For instance, if fewer HSCs choose to follow the RBCs roadmap, the individual will be prone to develop anemia. Abnormalities in the immune cell roadmap, on the other hand, have been associated with the onset of leukemia.

Epigenetic modulation in early hematopoiesis

The lab of Asifa Akhtar at the MPI of Immunobiology and Epigenetics in Freiburg investigates what governs the differentiation process of blood cells. Now, the teams has identified how the enzyme MOF, an epigenetic regulator, orchestrate the HSC fate in erythropoiesis.

"One of the most important intrinsic cues governing cell developmental processes is the modulation of the chromatin landscape," says Asifa Akhtar. In our cells, DNA is packaged around histone proteins to make the chromatin structure. This packaging plays a crucial role in cell type-specific gene regulation and, of course, also in erythroid differentiation. In its default state chromatin is not "permissive," meaning genes are switched off. But shifting histones opens the chromatin and promotes gene expression.

Epigenetic regulator guides HSCs on the right path

The enzyme MOF is known to directly trigger the "opening" of chromatin by acetylating the H4 histone on one specific site (K16ac). When the lab tracked the MOF occupancy during the erythropoiesis in mice, they found that the enzyme dynamically orchestrates erythropoiesis by regulating chromatin accessibility of HSCs and RBC progenitors. "Our data shows that the correct dosage and timing of Mof during blood cell development is essential to prime the chromatin for activation of the erythroid development program. This process ensures the correct transcription factor network that will be pivotal for the erythroid branch," says first-author Cecilia Pessoa Rodrigues.

The Max Planck researchers are convinced that these findings could mean considerable progress in our understanding of the erythroid lineage commitment and may give rise to new therapeutic approaches in diseases such as leukemia or anemia. Although the precise consequence of MOF depletion in humans remains unanswered, it is already known that a balanced and controlled activity of epigenetic regulators is essential for the normal development of hematopoietic cells. "It is not surprising that low levels of MOF are linked to acute myeloid leukemia (AML). We anticipate this could be explained by chromatin acetylation imbalance that is critical for relevant factors required for normal hematopoiesis. Revealing the right levels of chromatin accessibility and, subsequently, the gene regulatory mechanisms that fine-tune the differentiation trajectories will be insightful for further understanding of hematopoiesis in healthy and diseased states," says Asifa Akhtar.

 

 

 

 

Bottom top
Racist President and His More Racist Police

TEHRAN (FNA)- US President Donald Trump is facing an unprecedented revolt from the elite corps of ex-military leaders and presidents over his brazen response to mass protests and inflaming of racial divides. [VIDEO]
Fire, Tear Gas after Floyd Death: Continued Clashes Between Police, Protesters in US Cause Over 10,000 Arrested

TEHRAN (FNA)- Thousands arrested across US cities including, Los Angeles and New York amid the ongoing protests over the death of George Floyd, an unarmed Black man who died last week in police custody in Minneapolis, Minnesota. [VIDEO]
George Floyd: Protests Around World Show Solidarity with US Demonstrators

TEHRAN (FNA)- Thousands of people around the world have rallied in solidarity with anti-racism protests in the United States following the police killing of George Floyd on May 25. Floyd, an unarmed Black man, was pinned to the ground by a white officer in Minneapolis, Minnesota. The officer, who has since been fired and charged for murder, knelt on Floyd's neck for nearly nine minutes, as Floyd pleaded "I can't breathe". [PHOTOS]
Aftermath of Protests in Minneapolis

TEHRAN (FNA)- Community members help to clean up debris from buildings set on fire during protests in Minneapolis in reaction to the death of George Floyd in police custody. [PHOTOS]
Minneapolis in Turmoil after Police Killing of George Floyd

TEHRAN (FNA)- The city of Minneapolis has been wracked by days of protest after a white police officer kneeled on the neck of an unarmed black man for nearly nine minutes before he died. [PHOTOS]
Protests Over Killing of George Floyd Spread Worldwide, in Some of Them Police Clashes with Protesters

TEHRAN (FNA)- Protesters have marched in the US over the death of George Floyd at the hands of a police officer. Their anger over the killing of the unarmed black man has now spread worldwide. Over the weekend demonstrators gathered in UK, Netherlands, South Africa, Brazil, France and Greece to protest against police brutality in solidarity with the US crowds. In Greece, France and UK, police and protesters clashed and march for George Floyd turns violent. [VIDEO]
Death of George Floyd: Protesters Face Police Near White House

TEHRAN (FNA)- Protesters take to the streets chanting "no justice, no peace" as they stand in front of a line of police officers near the White House, in Washington, DC, which is under curfew for a fifth night. [VIDEO]
George Floyd Death: Protests Continue as US Defense Secretary Rejects Trump’s Demand for Troops

TEHRAN (FNA)- Protests over the death of George Floyd continued across the US on Wednesday, after a largely peaceful night. As demonstrators returned to the streets, police chiefs called for reform – and the US secretary of defense publicly rejected Donald Trump’s threat to deploy combat troops. [PHOTOS]
Rouhani Orders Central Bank to Take Immediate Measures to Unfreeze Iran's Assets in Foreign Banks

TEHRAN (FNA)- President Hassan Rouhani instructed the Central Bank of Iran (CBI) to do its best to release part of Iran's forex resources blocked in foreign banks.
Foreign Ministry Releases Details of Iranian Ship's Sinking in Iraqi Port

TEHRAN (FNA)- The Iranian Foreign Ministry issued an initial report on a cargo ship that sank off the Iraqi port of Umm Qasr early Friday.
Iran, Serbia Eyeing to Boost Transport Cooperation

TEHRAN (FNA)- Iranian Ambassador to Belgrade Rashid Hassanpour and Serbian Minister of Construction, Transport and Infrastructure Zorana Z. Mihajlović stressed developing cooperation in air and road transportation fields.
Iran Reports 2,886 New Coronavirus Cases, No Deaths in 13 Provinces

TEHRAN (FNA)- The Iranian health ministry announced on Friday that 2,886 new cases of infection to coronavirus have been diagnosed in the country in the past 24 hours, noting that no deaths has been reported in 13 provinces.
Iran Calls for Removal of Inhumane Sanctions against Syria

TEHRAN (FNA)- Iranian Foreign Ministry Spokesman Seyed Abbas Mousavi stressed Tehran’s support for Syria, and urged lifting of all sanctions that have impeded Damascus' endeavors to reconstruct the war-ravaged country.
Iran, UAE Resume Marine Trade Ties

TEHRAN (FNA)- Iran and the United Arab Emirates (UAE) have resumed their trade exchanges via sea, a provincial official announced.
Iran’s Mining Sector Sees 60% Investment Surge in Defiance of US Sanctions

TEHRAN (FNA)- Iranian mining sector had a significant hike in investment for new projects despite American sanctions that have been imposed on sales of expensive metals among other lucrative areas, said a spokesperson with IMIDRO.