Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells

Christensen, J. H.; Weissman, Irving L.

doi:10.1073/pnas.261562798

Cited by 677 publications

(634 citation statements)

References 42 publications

(34 reference statements)

Supporting

Mentioning

599

Contrasting

Unclassified

Order By: Relevance

“…To test whether this population (LT-HSC) was affected by PTH treatment, we evaluated the LKS fraction that was negative for the CD135 molecule (Lin À CD117 þ Sca-1 þ CD135 À ). (26)(27)(28) The distribution of this population followed the same changes observed for the LKS population with an almost significant increase in its percentage on day 7 (control ¼ 0.201 AE 0.031 versus PTH ¼ 0.280 AE 0.024, p ¼ .051) and no significant changes in absolute number. In contrast, on day 14 of PTH treatment, there was an increase in both the percentage (control ¼ 0.084 AE 0.008 versus PTH ¼ 0.144 AE 0.022, p ¼ .02) and absolute number (control ¼ 4.7 Â 10 5 AE 4.91 Â 10 3 versus PTH ¼ 7.2 Â 10 4 AE 1.01 Â 10 4 , p ¼ .03) of LT-HSC.…”

Section: Resultssupporting

confidence: 66%

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Parathyroid hormone (PTH) increases both the number of osteoclast in bone and the number of early hematopoietic stem cells (HSCs) in bone marrow. We previously characterized the phenotype of multiple populations of bone marrow cells with in vitro osteoclastogenic potential in mice. Here we examined whether intermittent administration of PTH influences these osteoclast progenitor (OCP) populations. C57BL/6 mice were treated with daily injections of bPTH(1-34) (80 mg/kg/day) for 7 or 14 days. We found that PTH caused a significant increase in the percentage of TN/CD115 þ CD117 high and TN/CD115 þ CD117 int cells ( p < .05) in bone marrow on day 7. In contrast, PTH decreased the absolute number of TN/CD115 þ CD117 low cells by 39% on day 7 ( p < .05). On day 14, there was no effect of PTH on osteoclast progenitor distribution in vivo. However, PTH treatment for 7 and 14 days did increase receptor activator of NF-kB ligand (RANKL)-and macrophage colony-stimulating factor (M-CSF)-stimulated in vitro osteoclastogenesis and bone resorption in TN/ CD115 þ cells. In the periphery, 14 days of treatment increased the percentage and absolute numbers of HSCs (Lin À CD117 þ Sca-1 þ ) in the spleen ( p < .05). These data correlated with an increase in the percent and absolute numbers of HSCs in bone marrow on day 14 ( p < .05). Interestingly, the effects on hematopoietic progenitors do not depend on osteoclast resorption activity. These results suggest that in vivo PTH treatment increased in vitro osteoclastogenesis and resorption without altering the number of osteoclast precursors. This implies that in vivo PTH induces sustained changes, possibly through an epigenetic mechanism, in the in vitro responsiveness of the cells to M-CSF and RANKL. ß

show abstract

Section: Resultssupporting

confidence: 66%

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Jacome-Galarza

Lee

Lorenzo

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…30,31 There is evidence that the FLT3-expressing fraction of HSPCs is characterized by short-term engrafting or low-quality stem cells. 22 FL has the biggest effect on primitive hematopoietic progenitor cells. 8 Studies have demonstrated that leukemias arise from a very small population of cells, termed leukemia stem cells (LSCs), that gain indefinite proliferation potential through accumulating mutations in normal HSCs or committed progenitor cells.…”

Section: Activated Flt3 Expression Increases the Stem Cell/ Progenitomentioning

confidence: 99%

“…20,21 Previous results suggest that early progenitor cells (CFC-GEMM) might be more dependent on the putative signaling function of the FLT3 kinase. 16,22 The type III tyrosine kinase receptor family, consisting of five membersFFLT3, KIT, FMS, and two genes for PDGFRFis characterized by five immunoglobulin-like folds in the extracellular domain, a single transmembrane domain and an interrupted tyrosine kinase domain in the intracellular region. 23,24 Tel is a member of the ETS family of transcriptional factors and is reported to be involved in several chromosomal translocations producing fusion proteins such as Tel-PDGFR in CMML, Tel-ABL in AML and Tel-JAK2 in ALL, all of which result in activated tyrosine kinase domains and cause transformation when expressed in hematopoietic cells.…”

Section: Introductionmentioning

confidence: 99%

Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease

et al. 2007

Leukemia

View full text Add to dashboard Cite

Evidence is continuing to accumulate that the FMS-like tyrosine kinase 3 (FLT3) receptor plays an important role in acute leukemias. Acute myeloid leukemia patients often express constitutive active mutant forms of the receptor in their leukemic cells. A t(12;13)(p13;q12) translocation between Tel and the FLT3 receptor was recently described in a patient with myeloproliferative disease (MPD). Here a Tel-FLT3 construct mimicking this fusion protein was used to generate transgenic mice. The fusion protein was previously found to constitutively activate FLT3 signaling and transform Ba/F3 cells. Expression of the fusion protein in the transgenic mice was found in all tissues assayed including spleen, bone marrow (BM), thymus and liver. These mice developed splenomegaly and had a high incidence of MPD with extramedullary hematopoiesis in the liver and lymph nodes. Spleens also had increased dendritic and natural killer cell populations. In vitro analysis of the hematopoietic progenitor cells derived from Tel-FLT3 transgenic mice showed a significant increase in the number of CFU-GM in the BM, and CFU-GM, BFU-E and CFU-GEMM in the spleen. BM also showed significant increases of in vivo CFU-S colonies. Thus, transgenic mice expressing constitutively activated Tel-FLT3 develop MPD with a long latency and also result in the expansion of the hematopoietic stem/progenitor cells.

show abstract

“…Despite being enriched for stem cell activity however, only a minor subset (∼1/30) of KLS cells are in fact stem cells with long-term multi-lineage potential . We and others have shown that inclusion of additional cell surface markers such as CD34 (Osawa et al, 1996), and flk2 (Adolfsson et al, 2001;Christensen and Weissman, 2001) can be used to significantly further enrich for HSC activity. Staining the BM of young (3 months), mid-aged (12 months), and old (24 months) mice with these markers reveals 3 distinct subpopulations (KLS: flk2+CD34+, flk2−CD34+, and flk2−CD34−) (Fig.…”

Section: Expansion Of Lt-hsc With Age Is Cell Autonomousmentioning

confidence: 99%

Hematopoietic stem cell aging: Mechanism and consequence

Rossi

Bryder

Weissman

2007

Experimental Gerontology

121

View full text Add to dashboard Cite

Advancing age is frequented by the onset of a variety of hematological conditions characterized by diminished homeostatic control of blood cell production. The fact that upstream hematopoietic stem and progenitor cells are obligate mediators of homeostatic control of all blood lineages, has implicated the involvement of these cells in the pathophysiology of these conditions. Indeed, evidence from our group and others has suggested that two of the most clinically significant ageassociated hematological conditions, namely, the diminution of the adaptive immune system, and the elevated incidence of myeloproliferative diseases, have their origin in cell autonomous changes in the functional capacity of hematopoietic stem cells.

show abstract

Flk-2 is a marker in hematopoietic stem cell differentiation: A simple method to isolate long-term stem cells

Cited by 677 publications

References 42 publications

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow

Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease

Hematopoietic stem cell aging: Mechanism and consequence

Contact Info

Product

Resources

About