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Group detects new steps in hematopoiesis

Hematopoietic stem cells

in the bone marrow

Researchers say they have discovered previously undetected steps in hematopoiesis, establishing that a highly complex series of events determine the fate of closely related populations of blood progenitor cells.

Their study revealed thousands of differences in gene expression between blood cell types.

These differences result from many specific events that are crucial for normal blood development, and errors in this process can lead to blood disorders.

The researchers described their work in Science.

The team sequenced RNA from 8 primary human hematopoietic progenitor populations representing the classical myeloid commitment stages of hematopoiesis and the main lymphoid stage.

This revealed 6711 genes and 10,724 transcripts enriched in non-protein-coding elements at early stages of differentiation.

The researchers also discovered the extent to which RNA is cut and pasted together in different ways during hematopoiesis, leading to specific forms of proteins for each of these stages.

“We have identified thousands of novel places where the RNA is processed in an alternative way,” said study author Willem Ouwehand, MD, PhD, of the University of Cambridge in the UK.

Specifically, the team identified 7881 novel splice junctions and 2301 differentially used alternative splicing events enriched in genes involved in regulatory processes.

“Such events changed the amount, structure, and behavior of proteins derived from a single gene,” said study author Wendy Erber, MD, DPhil, of the University of Western Australia in Crawley.

“Alternative proteins could drive stem cells towards becoming different mature blood cells.”

Until this study, hematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.

The researchers illustrated the importance of alternative RNA splicing in blood cell development by studying the role that 2 different forms of the same transcription factor—NFIB—play in megakaryocyte formation.

The team said their findings could have significant applications for patients with blood disorders. The results could aid the design of diagnostics and new therapies, as well as prove valuable for studies in stem cell transplant and for discovering the genetic basis of rare, inherited hematologic disorders.

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Hematopoietic stem cells

in the bone marrow

Researchers say they have discovered previously undetected steps in hematopoiesis, establishing that a highly complex series of events determine the fate of closely related populations of blood progenitor cells.

Their study revealed thousands of differences in gene expression between blood cell types.

These differences result from many specific events that are crucial for normal blood development, and errors in this process can lead to blood disorders.

The researchers described their work in Science.

The team sequenced RNA from 8 primary human hematopoietic progenitor populations representing the classical myeloid commitment stages of hematopoiesis and the main lymphoid stage.

This revealed 6711 genes and 10,724 transcripts enriched in non-protein-coding elements at early stages of differentiation.

The researchers also discovered the extent to which RNA is cut and pasted together in different ways during hematopoiesis, leading to specific forms of proteins for each of these stages.

“We have identified thousands of novel places where the RNA is processed in an alternative way,” said study author Willem Ouwehand, MD, PhD, of the University of Cambridge in the UK.

Specifically, the team identified 7881 novel splice junctions and 2301 differentially used alternative splicing events enriched in genes involved in regulatory processes.

“Such events changed the amount, structure, and behavior of proteins derived from a single gene,” said study author Wendy Erber, MD, DPhil, of the University of Western Australia in Crawley.

“Alternative proteins could drive stem cells towards becoming different mature blood cells.”

Until this study, hematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.

The researchers illustrated the importance of alternative RNA splicing in blood cell development by studying the role that 2 different forms of the same transcription factor—NFIB—play in megakaryocyte formation.

The team said their findings could have significant applications for patients with blood disorders. The results could aid the design of diagnostics and new therapies, as well as prove valuable for studies in stem cell transplant and for discovering the genetic basis of rare, inherited hematologic disorders.

Hematopoietic stem cells

in the bone marrow

Researchers say they have discovered previously undetected steps in hematopoiesis, establishing that a highly complex series of events determine the fate of closely related populations of blood progenitor cells.

Their study revealed thousands of differences in gene expression between blood cell types.

These differences result from many specific events that are crucial for normal blood development, and errors in this process can lead to blood disorders.

The researchers described their work in Science.

The team sequenced RNA from 8 primary human hematopoietic progenitor populations representing the classical myeloid commitment stages of hematopoiesis and the main lymphoid stage.

This revealed 6711 genes and 10,724 transcripts enriched in non-protein-coding elements at early stages of differentiation.

The researchers also discovered the extent to which RNA is cut and pasted together in different ways during hematopoiesis, leading to specific forms of proteins for each of these stages.

“We have identified thousands of novel places where the RNA is processed in an alternative way,” said study author Willem Ouwehand, MD, PhD, of the University of Cambridge in the UK.

Specifically, the team identified 7881 novel splice junctions and 2301 differentially used alternative splicing events enriched in genes involved in regulatory processes.

“Such events changed the amount, structure, and behavior of proteins derived from a single gene,” said study author Wendy Erber, MD, DPhil, of the University of Western Australia in Crawley.

“Alternative proteins could drive stem cells towards becoming different mature blood cells.”

Until this study, hematopoiesis was relatively well understood at the level of DNA. What was not known was how the genetic information in DNA was then transcribed to generate RNA, leading to protein formation.

The researchers illustrated the importance of alternative RNA splicing in blood cell development by studying the role that 2 different forms of the same transcription factor—NFIB—play in megakaryocyte formation.

The team said their findings could have significant applications for patients with blood disorders. The results could aid the design of diagnostics and new therapies, as well as prove valuable for studies in stem cell transplant and for discovering the genetic basis of rare, inherited hematologic disorders.

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