New blood: Tracing the beginnings of hematopoietic stem cells

August 14, 2014
New blood: Tracing the beginnings of hematopoietic stem cells
A scanning electron micrograph of a red blood cell, a platelet and a white blood cell. Credit: UC San Diego School of Medicine

Hematopoietic stem cells (HSCs) give rise to all other blood cell types, but their development and how their fate is determined has long remained a mystery. In a paper published online this week in Nature, researchers at the University of California, San Diego School of Medicine elaborate upon a crucial signaling pathway and the role of key proteins, which may help clear the way to generate HSCs from human pluripotent precursors, similar to advances with other kinds of tissue stem cells.

Principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine, and colleagues focused on the Notch signaling pathway, a system found in all animals and known to be critical to the generation of HSCs in vertebrates. "Notch signaling between emitting and receiving cells is key to establishing HSC fate during development," said Traver. "What has not been known is where, when and how Notch signal transduction is mediated."

Traver and colleagues discovered that the Notch signal is transduced into HSC precursor cells from signal emitting cells in the somite – embryologic tissues that eventually contribute to development of major body structures, such as skeleton, muscle and connective tissues – much earlier in the process than previously anticipated.

More specifically, they found that JAM proteins, best known for helping maintain tight junctions between to prevent vascular leakage, were key mediators of Notch signaling. When the researchers caused loss of function in JAM proteins in a zebrafish model, Notch signaling and HSCs were also lost. When they enforced Notch signaling through other means, HSC development was rescued.

"To date, it has not been possible to generate HSCs de novo from human pluripotent precursors, like induced pluripotent stem cells," said Traver. "This has been due in part to a lack of understanding of the complete set of factors that the embryo uses to make HSCs in vivo. It has also likely been due to not knowing in what order each required factor is needed."

"Our studies demonstrate that Notch signaling is required much earlier than previously thought. In fact, it may be one of the earliest determinants of HSC fate. This finding strongly suggests that in vitro approaches to instruct HSC fate from induced must focus on the Notch pathway at early time-points in the process. Our findings have also shown that JAM proteins serve as a sort of co-receptor for Notch signaling in that they are required to maintain close contact between signal-emitting and signal-receiving cells to permit strong activation of Notch in the precursors of HSCs."

The findings may have far-reaching implications for eventual development of hematopoietic stem cell-based therapies for diseases like leukemia and congenital blood disorders. Currently, it is not possible to create HSCs from differentiation of or induced pluripotent – pluripotent cells artificially derived from non-, such as skin cells – that are being used in other therapeutic research efforts.

Explore further: Cell discovery brings blood disorder cure closer

More information: Jam1a - Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling, Nature, DOI: 10.1038/nature13623

Related Stories

Cell discovery brings blood disorder cure closer

August 13, 2014
A cure for a range of blood disorders and immune diseases is in sight, according to scientists who have unravelled the mystery of stem cell generation.

Stem cell study finds source of earliest blood cells during development

March 21, 2014
Hematopoietic stem cells are now routinely used to treat patients with cancers and other disorders of the blood and immune systems, but researchers knew little about the progenitor cells that give rise to them during embryonic ...

Study unlocks origins of blood stem cells

December 9, 2011
A research team led by Nancy Speck, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, has discovered a molecular marker for the immediate precursors of ...

Novel marker discovered for stem cells derived from human umbilical cord blood

April 17, 2014
The development of stem cell therapies to cure a variety of diseases depends on the ability to characterize stem cell populations based on cell surface markers. Researchers from the Finnish Red Cross have discovered a new ...

Recommended for you

Female mouse embryos actively remove male reproductive systems

August 17, 2017
A protein called COUP-TFII determines whether a mouse embryo develops a male reproductive tract, according to researchers at the National Institutes of Health and their colleagues at Baylor College of Medicine, Houston. The ...

Two-step process leads to cell immortalization and cancer

August 17, 2017
A mutation that helps make cells immortal is critical to the development of a tumor, but new research at the University of California, Berkeley suggests that becoming immortal is a more complicated process than originally ...

New Pathology Atlas maps genes in cancer to accelerate progress in personalized medicine

August 17, 2017
A new Pathology Atlas is launched today with an analysis of all human genes in all major cancers showing the consequence of their corresponding protein levels for overall patient survival. The difference in expression patterns ...

New technique overcomes genetic cause of infertility

August 17, 2017
Scientists have created healthy offspring from genetically infertile male mice, offering a potential new approach to tackling a common genetic cause of human infertility.

Are stem cells the link between bacteria and cancer?

August 17, 2017
Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, ...

Inhibiting a protein found to reduce progression of Alzheimer's and ALS in mice

August 17, 2017
(Medical Xpress)—A team of researchers with Genetech Inc. and universities in Hamburg and San Francisco has found that inhibiting the creation of a protein leads to a reduction in the progression of Alzheimer's disease ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.