32 research outputs found
PDGFRα and CD51 mark human Nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion
Low RPS14 expression is common in myelodysplastic syndromes without 5q- aberration and defines a subgroup of patients with prolonged survival
This paper shows that the expression of the ribosomal protein S14 (RPS14) is reduced in about two thirds of patients with non-5q- myelodysplastic syndrome. See related perspective article on page 1336
Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.
Poor prognosis for patients after myelo- and non-myeloablative conditioning therapy followed by allogeneic peripheral blood stem cell transplantation admitted to Intensive Care Unit
Poor prognosis for patients after myelo- and non-myeloablative conditioning therapy followed by allogeneic peripheral blood stem cell transplantation admitted to Intensive Care Unit
Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion
In the bone marrow, hematopoietic stem cells (HSCs) lodge in specialized microenvironments that tightly control the proliferative state of HSCs to adapt to the varying needs for replenishment of blood cells while also preventing HSC exhaustion. All putative niche cells suggested thus far have a nonhematopoietic origin. Thus, it remains unclear how feedback from mature cells is conveyed to HSCs to adjust their proliferation. Here we show that megakaryocytes (MKs) can directly regulate HSC pool size in mice. Three-dimensional whole-mount imaging revealed that endogenous HSCs are frequently located adjacent to MKs in a nonrandom fashion. Selective in vivo depletion of MKs resulted in specific loss of HSC quiescence and led to a marked expansion of functional HSCs. Gene expression analyses revealed that MKs are the source of chemokine C-X-C motif ligand 4 (CXCL4, also named platelet factor 4 or PF4) in the bone marrow, and we found that CXCL4 regulates HSC cell cycle activity. CXCL4 injection into mice resulted in a reduced number of HSCs because of their increased quiescence. By contrast, Cxcl4(-/-) mice exhibited an increased number of HSCs and increased HSC proliferation. Combined use of whole-mount imaging and computational modeling was highly suggestive of a megakaryocytic niche capable of independently influencing HSC maintenance by regulating quiescence. These results indicate that a terminally differentiated cell type derived from HSCs contributes to the HSC niche, directly regulating HSC behavior