Abstract：
:Lifelong blood production is ensured by a population of rare and largely quiescent, long-lived hematopoietic stem cells (HSCs). The advent of single-cell technologies has recently highlighted underlying molecular and functional heterogeneity within the HSC pool. Despite heterogenous HSC behaviors, quiescence remains as the most uncontroversial and unifying property of HSCs. Nonetheless, a multifaceted and complex continuum of states has recently been identified within what was previously described as just "quiescent." Here we review such evidence and discuss how it challenges preconceived ideas on the contribution of cell cycle kinetics to HSC function. Specifically, we detail how both the frequency and kinetics of HSC division, largely determined by a network of molecular regulators linked to early G1, influence long-term HSC functionin vivo. In addition, we present data that indicate lengthening the duration of G1 by inhibiting CDK6 decreases lymphoid differentiation of a subset of lymphoid-primed human HSCs, thus linking cell cycle kinetics to cell fate decisions in HSCs. Finally, we reflect on how these new insights can be helpful to fully harness HSC potential in clinical applications that require ex vivo culture.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Johnson C,Belluschi S,Laurenti Edoi
10.1016/j.exphem.2020.11.003subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1-10.e2eissn
0301-472Xissn
1873-2399pii
S0301-472X(20)30621-4journal_volume
92pub_type
杂志文章,评审abstract：:Malignant osteopetrosis is a disorder characterized by a deficiency in osteoclast number or function. In one animal model of osteopetrosis, the op/op mouse, macrophage colony-stimulating factor (M-CSF) is absent, and the administration of M-CSF corrects the defects. We evaluated the serum of 13 patients with malignant...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:Neutropenia is common to both Hermansky-Pudlak syndrome type 2 and canine cyclic hematopoiesis (CH) which are caused by mutations in the AP3B1 gene. The purpose of this study was to determine if pearl mice were neutropenic. Complete blood counts (CBCs) and bone marrow differential counts, colony forming unit (CFU) ass...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.05.002
更新日期：2013-10-01 00:00:00
abstract：OBJECTIVE:To examine whether oncogenic Ras affects transforming growth factor (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream signal transduction pathway involved in the interference with TGF-beta-induced cell-cycle arrest. MATERIALS AND METHODS:Two leukemic cell lines bearing N-Ras(L61...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.04.006
更新日期：2005-07-01 00:00:00
abstract：OBJECTIVE:Activated platelets participate in inflammatory and microbicidal processes by upregulation of surface selectins, shedding of CD40 ligand, and release of platelet microbicidal proteins and microparticles. Given their myeloid lineage, we hypothesized that platelets express functional N-formyl peptide receptors ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.09.010
更新日期：2005-01-01 00:00:00
abstract：OBJECTIVE:All-trans retinoic acid (ATRA) has been used as the first-line therapy for patients with acute promyelocytic leukemia (APL). We previously reported that ATRA increased serum thrombopoietin (TPO) levels accompanied by thrombocytosis during ATRA therapy for APL. In this study, we investigated the mechanism of t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2003.10.009
更新日期：2004-01-01 00:00:00
abstract：OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00778-0
更新日期：2002-02-01 00:00:00
abstract：OBJECTIVE:Stem cell transplantation has a place in the management of many patients with hematological disorders, but is no longer the final and definitive treatment for most of these individuals. The relapsing patient may be offered further therapy, and evaluating the contribution of the treatments available has become...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.06.007
更新日期：2008-11-01 00:00:00
abstract：:Peripheral blood and bone marrow specimens from patients with polycythemia vera (PV) and chronic myelogenous leukemia (CML) were assayed for erythroid and granulopoietic progenitor cells. All compartments were increased in CML patients in relapse although the ratio of BFU-E to CFU-C numbers remained constant in all CM...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：:Adult hematological malignancies, such as acute myeloid leukemia, are thought to arise through the gradual acquisition of oncogenic mutations within long-lived hematopoietic stem cells (HSCs). Genomic analysis of peripheral blood DNA has recently identified leukemia-associated genetic mutations within otherwise health...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2019.08.004
更新日期：2019-09-01 00:00:00
abstract：:A fluorescence-activated cell sorter has been used to sort out enriched populations of murine hemopoietic stem cells from mouse bone marrow, based on fluorescence of cells labeled with various antisera. Significant positive enrichment for stem cells was obtained with rabbit anti-human brain, human anti-human sperm and...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-08-01 00:00:00
abstract：OBJECTIVE:Progenipoietin-1 is an agonist of both the granulocyte colony-stimulating factor and fetal liver tyrosine kinase-3 receptors capable of inducing the proliferation of multiple hematopoietic cell lineages. The potential of progenipoietin-1 to mobilize transplantable hematopoietic stem cells into the peripheral ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00675-0
更新日期：2001-08-01 00:00:00
abstract：:We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enha...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：:The reproducibility and utility of an in vitro bioassay for erythropoietin were evaluated, and modifications, including the use of frozen target cells, were made. The assay, based on 3H-thymidine incorporation into phenylhydrazine-treated mouse spleen cells, showed a dose-response curve from 0.2 to 20 mU of sheep plas...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-05-01 00:00:00
abstract：OBJECTIVE:The retroviral oncogene v-Cbl causes pre-B cell lymphomas and myeloid leukemias in mice, and its Drosophila homologue is oncogenic, causing enhanced receptor tyrosine kinase signaling. The human Cbl gene resides at 11q23. The aim of this study is to determine the effect of oncogenic Cbl on growth-regulating r...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(01)00647-6
更新日期：2001-06-01 00:00:00
abstract：:The retroviral vector N2, which is derived from the Moloney murine leukemia retrovirus, was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells from fetal, neonatal, and adult dogs and cats. Infection of canine and feline bone marrow cells ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Colony formation by megakaryocyte (MK) progenitors was studied in 36 normal individuals and in 26 patients with primary thrombocythemia (PT) using an improved plasma clot cloning system. MK colonies were identified by immunoperoxidase staining using a monoclonal antibody against human platelet glycoprotein IIb/IIIa co...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：OBJECTIVE:Umbilical cord blood (CB) provides an alternative source of hematopoietic progenitor cells for transplantation; however, prolonged thrombocytopenia remains a major obstacle due to the low numbers of megakaryocyte progenitor (Mk-prog) cells and their subsequent delayed engraftment. In this study, we improved t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00884-6
更新日期：2002-09-01 00:00:00
abstract：:The processing of inflammatory signals occurs through a variety of mechanisms; the recent descriptions of the tethered ligand receptor for thrombin (JA Hoxie et al., J Biol Chem 268:13756, and TK Vu et al., Cell 64:1057) provide a novel route and mechanism for cellular activation after inflammation and thrombosis. Usi...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult A...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.02.010
更新日期：2016-06-01 00:00:00
abstract：OBJECTIVE:We have previously shown that Flt3 ligand (FL)/Flt3 signaling regulates hematopoietic cell migration by modulating the SDF1alpha/CXCR4 signaling pathway. Herein, we evaluated whether a functional interaction between SDF1alpha/CXCR4 signaling and internal tandem duplication (ITD) of Flt3 regulates aberrant hem...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.001
更新日期：2006-08-01 00:00:00
abstract：OBJECTIVE:In utero hematopoietic cell transplantation (IUHCT) is a non-ablative approach that achieves mixed allogeneic chimerism and donor-specific tolerance. However, clinical application of IUHCT has been limited by minimal engraftment. We have previously demonstrated in the murine model that low-level allogeneic ch...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.11.011
更新日期：2006-03-01 00:00:00
abstract：:Washed canine platelets were shown to express a significant level of von Willebrand factor (vWf). Canine platelet vWf differed from canine plasma vWf by the absence of satellite bands associated with each multimer when resolved by SDS-agarose gel electrophoresis. Expression and multimeric composition of canine platele...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DN...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-09-01 00:00:00
abstract：UNLABELLED:In this paper we describe an experimental model for ex vivo purging of contaminating tumor cells from peripheral blood stem cell (PBSC) collections obtained from patients with acute myeloblastic leukemia (AML). We studied the combination of the alkylating agent nitrogen mustard (NM; concentrations ranging fr...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-11-01 00:00:00
abstract：OBJECTIVE:B-lineage acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphatic blastic phase in adults have poor prognoses despite intensive chemotherapy. Novel targeted treatment modalities emerge, but their evaluation requires relevant in vitro models of lymphoblastic leukemia. Presently available c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.11.002
更新日期：2009-03-01 00:00:00
abstract：:We present the first report of a T-helper cell line, HUT 102, constitutively producing both granulocyte-macrophage colony-stimulating factor (GM-CSF) and monocytic colony-stimulating factor (M-CSF), as detected by sensitive enzyme-linked immunosorbent assays and Northern blot analysis. However, neither amplification n...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：OBJECTIVES:We previously demonstrated that allogeneic bone marrow transplantation (BMT) after low-dose total lymphoid irradiation (200 cGy) and depletion of donor-reactive cells with cyclophosphamide (Cy) converted recipients to graft-vs-host disease (GVHD)-free chimeras tolerant to donor skin grafts. BMT also generate...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)01009-3
更新日期：2003-01-01 00:00:00
abstract：:The renal tumor RCC-3-JCK, when transplanted into immunodeficient mice, caused an erythrocytic polycythemia. When grown in culture, the tumor cells secreted a substance into the culture medium that chromatographed by size-exclusion high-performance liquid chromatography similarly to purified human erythropoietin (Ep) ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Initiation of DNA synthesis by recombinant colony-stimulating factors (CSFs) was assessed in normal human marrow blast cells isolated by expression of CD34 antigen (tritiated thymidine incorporation). Continuous exposure to CSF was required. A mild increase in DNA synthesis was initiated by granulocyte CSF (G-CSF; gre...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:The aim of this work was to monitor the functional and phenotypic variations of natural killer (NK) cells in seven children with stage IV neuroblastoma (NB) treated with recurrent 5-day cycles of interleukin-2 (IL-2) at a dose of 18 x 10(6) IU/m2/d by continuous intravenous infusion. All patients who entered the study...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
