title: Myeloid Cell Origins, Differentiation, and Clinical Implications.
abstract: The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the common myeloid progenitor and all of its resulting cell types. The stages of hematopoiesis have been defined in both mice and humans. During embryological development, the earliest hematopoiesis takes place in yolk sac blood islands and then migrates to the fetal liver and hematopoietic organs. Some adult myeloid populations develop directly from yolk sac progenitors without apparent bone marrow intermediates, such as tissue-resident macrophages. Hematopoiesis also changes over time, with a bias of the dominating HSCs toward myeloid development as animals age. Defects in myelopoiesis contribute to many hematologic disorders, and some of these can be overcome with therapies that target the aberrant stage of development. Furthermore, insights into myeloid development have informed us of mechanisms of programmed cell removal. The CD47/SIRPα axis, a myeloid-specific immune checkpoint, limits macrophage removal of HSCs but can be exploited by hematologic and solid malignancies. Therapeutics targeting CD47 represent a new strategy for treating cancer. Overall, an understanding of hematopoiesis and myeloid cell development has implications for regenerative medicine, hematopoietic cell transplantation, malignancy, and many other diseases.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.|Stanford Cancer Institute.|Ludwig Center for Cancer Stem Cell Research and Medicine.|Institute for Stem Cell Biology and Regenerative Medicine.
authors.forename: Kipp
authors.initials: K
authors.lastname: Weiskopf
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Ludwig Center for Cancer Stem Cell Research and Medicine.|Stanford Cancer Institute.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schnorr
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA 94305.|Stanford Cancer Institute.|Ludwig Center for Cancer Stem Cell Research and Medicine.
authors.forename: Wendy W
authors.initials: WW
authors.lastname: Pang
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Ludwig Center for Cancer Stem Cell Research and Medicine.|Stanford Cancer Institute.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Chao
authors.affiliation: Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Chhabra
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Ludwig Center for Cancer Stem Cell Research and Medicine.|Stanford Cancer Institute.
authors.forename: Jun
authors.initials: J
authors.lastname: Seita
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Ludwig Center for Cancer Stem Cell Research and Medicine.|Stanford Cancer Institute.
authors.forename: Mingye
authors.initials: M
authors.lastname: Feng
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine.|Ludwig Center for Cancer Stem Cell Research and Medicine.|Stanford Cancer Institute.
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D022423:Myeloid Cells / Q000166:cytology*