Author response: Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling
Year: 2015
Type: peer-review
Abstract: Bone marrow contains types of stem cell that can produce new blood and immune cells. Transplanting bone marrow from a healthy person can be used to treat people with certain disorders of the blood and immune system, by providing a new supply of regenerating bone marrow stem cells. Bone marrow transplants are also critical for individuals who had their own bone marrow stem cells destroyed by cancer or by toxic anti-cancer therapies like chemotherapy. Acquiring bone marrow for transplants can be a difficult process. Sometimes doctors can use the patient's own stem cells for a transplant. But in circumstances where the patient lacks healthy bone marrow, a bone marrow donor must be found. Donors and recipients must be carefully matched: certain proteins on the donor's bone marrow cells must be very similar to the proteins on the recipient's bone marrow cells, or the recipient's immune system will attack and kill the new cells. If scientists could learn to grow the stem cells found in bone marrow in laboratories, they could circumvent some of the challenges associated with bone marrow donation. To do that, scientists must first understand the precise molecular mechanisms that allow the blood cell-producing stem cells to regenerate themselves and produce new blood cells. Angiopoietin-like proteins are commonly used to help stem cells grow in the laboratory, and Lin et al. have now looked in detail at how these proteins work. This revealed that angiopoietin-like proteins also cause the stem cells that produce blood cells to grow in zebrafish embryos and are necessary for the embryos' vascular system to develop properly. Zebrafish embryos lacking angiopoietin-like proteins develop a similar set of developmental problems as zebrafish embryos with a mutation in another protein called Notch. Through a series of experiments, Lin et al. show that angiopoietin-like proteins interact with Notch and help transform Notch into its active form, which is necessary for blood stem cell growth. Lin et al. also found that both angiopoietin-like proteins and Notch affect the same signaling molecules. This suggests that the two proteins may work together as part of the same molecular pathway. The work suggests an alternative method to activate Notch for blood stem cell stimulation during processes such as bone marrow or cord blood transplantation.
Authors: Michelle I Lin, Emily N Price, Sonja Boatman, Elliott J Hagedorn, Eirini Trompouki, Sruthi Satishchandran, Charles W Carspecken, Audrey Uong, Anthony DiBiase, Song Yang, Matthew C Canver, Ann Dahlberg, Zhigang Lu, Cheng Cheng Zhang, Stuart H Orkin, Irwin D Bernstein, Jon C Aster, Richard M White, Leonard I Zon
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2987050367