163. POTENTIAL MARKERS FOR THE PROSPECTIVE ISOLATION OF HUMAN ENDOMETRIAL EPITHELIAL STEM/PROGENITOR CELLS

2010 ◽  
Vol 22 (9) ◽  
pp. 81
Author(s):  
C. E. Gargett ◽  
C. S. C. Tan ◽  
H. Buhring
Keyword(s):  
Progenitor Cells ◽  
Hormone Replacement ◽  
Proliferative Potential ◽  
Cell Marker ◽  
Self Renewal ◽  
Epithelial Cell Marker ◽  
Post Menopausal ◽  
Prospective Isolation

The human endometrium regenerates each month following menstruation, parturition and in post-menopausal women taking hormone replacement therapy. Adult stem/progenitor cells discovered residing in human and mouse endometrium may be responsible for this regenerative capacity. However, assays used to identify these stem/progenitor cells are retrospective. The aim of this study is to identify surface markers for the prospective isolation of human endometrial epithelial progenitor cells using a panel of 22 antibodies. Flow cytometry and was used in the initial screen and immunohistochemistry was used to reveal the location of marker expression. Multi-colour FACS protocols were developed with promising markers in conjunction with EpCAM (epithelial cell marker) and to exclude endothelial (CD31+), leukocytes (CD45+) and stromal (CD90+) cells. Sorted subpopulations were assessed for clonogenicity and self-renewal activity using in vitro cloning assays. Six antibodies were short-listed. 2D1D12 enriched for progenitor cells that formed epithelial clones in culture (n = 2). The 2D1D12+EpCAM+ fraction produced very few colony-forming units (CFU). 2D1D12–EpCAM+ fraction gave rise to small CFU. However the 2D1D12+EpCAM– population showed the greatest progenitor activity, producing many large CFU that could be serially cloned twice, indicating self renewal activity. This preliminary data suggests that 2D1D12+EpCAM–CD90–CD31–CD45– population may enrich for human endometrial epithelial stem/progenitor cells. Importantly, large CFU have previously been reported to exhibit stem cell properties of self-renewal, differentiation and high proliferative potential (1). Future studies will focus on xenografting this population to assess tissue reconstitution ability in vivo. The identification of endometrial epithelial stem/progenitor cell marker(s) will enable their prospective isolation for further characterisation and will assist in the investigation of their potential role in endometrial proliferative disorders such as endometriosis and endometrial cancer. (1) Gargett CE et al (2009) Biol Reprod 80: 1136–45.

scholarly journals Hematopoietic stem/progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4773-4777 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Man-Ryul Lee ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
Nutan Prasain ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Immunodeficient Mice ◽  
Induced Pluripotent

Abstract Cryopreservation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) is crucial for cord blood (CB) banking and transplantation. We evaluated recovery of functional HPC cryopreserved as mononuclear or unseparated cells for up to 23.5 years compared with prefreeze values of the same CB units. Highly efficient recovery (80%-100%) was apparent for granulocyte-macrophage and multipotential hematopoietic progenitors, although some collections had reproducible low recovery. Proliferative potential, response to multiple cytokines, and replating of HPC colonies was extensive. CD34+ cells isolated from CB cryopreserved for up to 21 years had long-term (≥ 6 month) engrafting capability in primary and secondary immunodeficient mice reflecting recovery of long-term repopulating, self-renewing HSCs. We recovered functionally responsive CD4+ and CD8+ T lymphocytes, generated induced pluripotent stem (iPS) cells with differentiation representing all 3 germ cell lineages in vitro and in vivo, and detected high proliferative endothelial colony forming cells, results of relevance to CB biology and banking.

Enforced expression of cyclin D2 enhances the proliferative potential of myeloid progenitors, accelerates in vivo myeloid reconstitution, and promotes rescue of mice from lethal myeloablation

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 986-992 ◽  
Author(s):  
Yutaka Sasaki ◽  
Christina T. Jensen ◽  
Stefan Karlsson ◽  
Sten Eirik W. Jacobsen
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Proliferative Potential ◽  
Cyclin D2 ◽  
Hematopoietic Stem ◽  
Murine Bone Marrow ◽  
Myeloid Progenitors

AbstractSevere and prolonged cytopenias represent a considerable problem in clinical stem cell transplantations. Cytokine-induced ex vivo expansion of hematopoietic stem and progenitor cells has been intensively explored as a means of accelerating hematopoietic recovery following transplantation but have so far had limited success. Herein, overexpression of D-type cyclins, promoting G0/G1 to S transition, was investigated as an alternative approach to accelerate myeloid reconstitution following stem cell transplantation. With the use of retroviral-mediated gene transfer, cyclin D2 was overexpressed in murine bone marrow progenitor cells, which at limited doses showed enhanced ability to rescue lethally ablated recipients. Competitive repopulation studies demonstrated that overexpression of cyclin D2 accelerated myeloid reconstitution following transplantation, and, in agreement with this, cyclin D2–transduced myeloid progenitors showed an enhanced proliferative response to cytokines in vitro. Furthermore, cyclin D2–overexpressing myeloid progenitors and their progeny were sustained for longer periods in culture, resulting in enhanced and prolonged granulocyte production in vitro. Thus, overexpression of cyclin D2 confers myeloid progenitors with an enhanced proliferative and granulocyte potential, facilitating rapid myeloid engraftment and rescue of lethally ablated recipients.

scholarly journals Humanized large-scale expanded endothelial colony–forming cells function in vitro and in vivo

Blood ◽  
2009 ◽  
Vol 113 (26) ◽  
pp. 6716-6725 ◽  
Author(s):  
Andreas Reinisch ◽  
Nicole A. Hofmann ◽  
Anna C. Obenauf ◽  
Karl Kashofer ◽  
Eva Rohde ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Large Scale ◽  
Proliferative Potential ◽  
Vascular Networks ◽  
Endothelial Progenitor ◽  
Endothelial Colony Forming Cells ◽  
Promising Tool

Abstract Endothelial progenitor cells are critically involved in essential biologic processes, such as vascular homeostasis, regeneration, and tumor angiogenesis. Endothelial colony–forming cells (ECFCs) are endothelial progenitor cells with robust proliferative potential. Their profound vessel-forming capacity makes them a promising tool for innovative experimental, diagnostic, and therapeutic strategies. Efficient and safe methods for their isolation and expansion are presently lacking. Based on the previously established efficacy of animal serum–free large-scale clinical-grade propagation of mesenchymal stromal cells, we hypothesized that endothelial lineage cells may also be propagated efficiently following a comparable strategy. Here we demonstrate that human ECFCs can be recovered directly from unmanipulated whole blood. A novel large-scale animal protein-free humanized expansion strategy preserves the progenitor hierarchy with sustained proliferation potential of more than 30 population doublings. By applying large-scale propagated ECFCs in various test systems, we observed vascular networks in vitro and perfused vessels in vivo. After large-scale expansion and cryopreservation phenotype, function, proliferation, and genomic stability were maintained. For the first time, proliferative, functional, and storable ECFCs propagated under humanized conditions can be explored in terms of their therapeutic applicability and risk profile.

Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1525-1531 ◽  
Author(s):  
David A. Ingram ◽  
Noel M. Caplice ◽  
Mervin C. Yoder
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Circulating Endothelial Cells ◽  
Proliferative Potential ◽  
Endothelial Progenitor ◽  
Detailed Understanding ◽  
Circulating Endothelial Progenitor Cells

Abstract The field of vascular biology has been stimulated by the concept that circulating endothelial progenitor cells (EPCs) may play a role in neoangiogenesis (postnatal vasculogenesis). One problem for the field has been the difficulty in accurately defining an EPC. Likewise, circulating endothelial cells (CECs) are not well defined. The lack of a detailed understanding of the proliferative potential of EPCs and CECs has contributed to the controversy in identifying these cells and understanding their biology in vitro or in vivo. A novel paradigm using proliferative potential as one defining aspect of EPC biology suggests that a hierarchy of EPCs exists in human blood and blood vessels. The potential implications of this view in relation to current EPC definitions are discussed.

Abstract 464: Cellular and Molecular Characterisation of Human Endothelial Progenitors in vivo Defined Based on Self-Renewal and Colony Forming Potential Identifies Notch Signaling as a Key Pathway

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jatin Patel ◽  
Abbas Shafiee ◽  
Ho Yi Wong ◽  
Josue Alexis ◽  
Kiarash Khosrotehrani
Keyword(s):  
Molecular Level ◽  
Notch Signalling ◽  
Proliferative Potential ◽  
Cell Type ◽  
Self Renewal ◽  
Endothelial Progenitors ◽  
Key Driver ◽  
Single Cell Culture

Background: Although endothelial progenitors have long been described, there remains significant controversy around their identity in vivo . The endothelial colony forming (ECFC) assays suggested a hierarchy among endothelial cells in vivo . Our aim was to systematically test different endothelial cell populations sorted from the human placenta, a highly vascularised tissue, based on various cell surface markers for their ECFC potential. Methods and Results: Upon sorting based on key markers CD45, CD34 and CD34 it was easily established that most ECFC potential was concentrated in the CD45-CD34+ fraction. Among this population, single cell culture assays (>300 wells per cell type) were performed on sorted CD31neg, CD31int and CD31hi cells. Only the CD31int cells were able to grow high proliferative potential ECFC. CD31neg populations contained mesenchymal stem cells (MSC) whereas CD31hi cells only produced mature endothelial clusters. RNA sequencing of each fraction identified Notch signalling as a key driver of endothelial progenitors as opposed to MSC. When the CD31int population was further characterised it was found to be expressing VE-Cadherin as predicted by the RNAseq, however, was not in contact with the circulation as it did not stain for lectins injected intravenously. In accordance the self-renewing fraction of ECFC cultures in vitro was dependent on Notch signalling and controlled the expression of IL33 and CDKN1C (p57) to maintain progenitors in quiescence. This was validated in vitro and in vivo by performing shRNA and pharmacological inhibition of the different pathways. Conclusion: Our study uncovers a population of endothelial progenitors in vivo at the cellular and molecular level and identified a novel role for Notch signalling in maintaining progenitor self-renewal in vivo and in vitro .

Oncogenic Wilms Tumor 1 (WT1) Mutation Augments Hematopoietic Progenitor Cell Clonogenicity and Promotes Expansion Of The Long-Term Hematopoietic Stem Cell (LT-HSC) Compartment: Implications For WT1-Mediated Leukemogenesis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1269-1269
Author(s):  
Colleen E. Annesley ◽  
Rachel E. Rau ◽  
Daniel Magoon ◽  
David Loeb ◽  
Patrick Brown
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Wilms Tumor ◽  
Wild Type ◽  
Hematopoietic Progenitor ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Exon 9

Abstract Background The WT1 gene encodes for a zinc finger-containing transcription factor involved in differentiation, cell cycle regulation and apoptosis. WT1 expression is developmentally regulated and tissue-specific, with expression maintained in the kidney and in CD34+ hematopoietic progenitor cells. Inactivating mutations of this tumor suppressor gene are well-described in sporadic Wilms tumor and as germline mutations in Wilms tumor predisposition syndromes. WT1 mutations have been reported in approximately 10% of both adult and pediatric patients with cytogenetically-normal acute myeloid leukemia (CN-AML), and have been associated with treatment failure and a poor prognosis. These reported mutations consist of insertions, deletions or point mutations. Many are frameshift mutations in exon 7, can occur as biallelic double mutations, and result in truncated proteins which may alter DNA-binding ability. Missense mutations in exon 9 have also been identified, and reports suggest that these may act in a dominant-negative manner, resulting in a loss of function. Despite these observations, the functional contribution of WT1 mutations to leukemogenesis is still largely undetermined. Methods/Results We obtained a novel knock-in WT1 mutant mouse model, which is heterozygous for the missense mutation R394W in exon 9, and homologous to exon 9 mutations seen in human AML. We hypothesized that WT1 mutations may have an aberrant effect on hematopoiesis, and specifically, could alter progenitor cell differentiation or proliferation. To investigate this, we collected lineage-negative bone marrow (lin- BM) cells from two-month old WT1 mutant (WT1mut) and wild-type (wt) mice. We performed methylcellulose colony-forming assays, serially replating cells every 10-12 days. Strikingly, WT1mut progenitor cells showed higher in vitro colony-forming capacity and an increased ability to serially replate, suggesting aberrantly enhanced self-renewal capability. Furthermore, WT1mut colonies from secondary and tertiary passages were larger and more cohesive than wild-type colonies, demonstrating increased proliferation and morphology consistent with blast colony-forming units (CFU-blast). Flow cytometric analysis of these WT1mut cells at tertiary replating revealed an immature, largely c-Kit+ population. Next, in order to study the effects of WT1mut on HSCs in vivo, we performed serial competitive transplantation of HSC-enriched, lineage-depleted BM into lethally irradiated mice. At 14 weeks post-transplant, the donor bone marrow cells were harvested and analyzed by flow cytometry. We observed a significant expansion of the LT-HSC compartment in the WT1mut mice compared to wild-type mice. These data provide new insight into the biology and functional role of WT1 mutations in the aberrant regulation of hematopoietic stem and progenitor cell expansion. Conclusion Oncogenic WT1 mutations confer enhanced proliferation and renewal of myeloid progenitor cells in vitro and expansion of LT-HSCs in vivo. Our findings suggest that WT1 mutations enhance stem cell self-renewal, potentially priming these cells for leukemic transformation upon acquisition of cooperative events. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Conditional Activation of Bmi1 Expression Regulates Self-renewal, Apoptosis, and Differentiation of Neural Stem/Progenitor Cells In Vitro and In Vivo

Stem Cells ◽  
2011 ◽  
Vol 29 (4) ◽  
pp. 700-712 ◽  
Author(s):  
Gokhan Yadirgi ◽  
Veronica Leinster ◽  
Serena Acquati ◽  
Heeta Bhagat ◽  
Olga Shakhova ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Self Renewal ◽  
Bmi1 Expression ◽  
Neural Stem Progenitor Cells

Human hematopoietic stem/progenitor cells overexpressing Smad4 exhibit impaired reconstitution potential in vivo

Blood ◽  
2012 ◽  
Vol 120 (22) ◽  
pp. 4343-4351 ◽  
Author(s):  
Emma Rörby ◽  
Matilda Nifelt Hägerström ◽  
Ulrika Blank ◽  
Göran Karlsson ◽  
Stefan Karlsson
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Cell System ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Smad Pathway ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Abstract Hematopoietic stem cells (HSCs) constitute a rare population of tissue-specific cells that can self-renew and differentiate into all lineages of the blood cell system. These properties are critical for tissue regeneration and clinical applications of HSCs. Cord blood is an easily accessible source of HSCs. However, the number of HSCs from one unit is too low to effectively transplant most adult patients, and expansion of HSCs in vitro has met with limited success because of incomplete knowledge regarding mechanisms regulating self-renewal. Members of the TGF-β superfamily have been shown to regulate HSCs through the Smad signaling pathway; however, its role in human HSCs has remained relatively uncharted in vivo. Therefore, we asked whether enforced expression of the common-Smad, Smad4, could reveal a role for TGF-β in human hematopoietic stem/progenitor cells (HSPCs) from cord blood. Using a lentiviral overexpression approach, we demonstrate that Smad4 overexpression sensitizes HSPCs to TGF-β, resulting in growth arrest and apoptosis in vitro. This phenotype translates in vivo into reduced HSPC reconstitution capacity yet intact lineage distribution. This suggests that the Smad pathway regulates self-renewal independently of differentiation. These findings demonstrate that the Smad signaling circuitry negatively regulates the regeneration capacity of human HSPCs in vivo.

Constitutive Expression of the ABCG2 (BCRP), the Molecular Determinant of the Side Population, Increases the Proliferative Potential of Human Clonogenic Progenitors and Supports Human Myeloid Engraftment in the NOD/SCID Mouse Model.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 799-799
Author(s):  
Farid Ahmed ◽  
Natalia Arseni ◽  
Wolfgang Hiddemann ◽  
Christian Buske ◽  
Michaela Feuring-Buske
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Side Population ◽  
Myeloid Cells ◽  
Constitutive Expression ◽  
Fold Increase ◽  
Proliferative Potential ◽  
Molecular Determinant

Abstract Adult hematopoietic stem cells can be identified by the ability to rapidly efflux the Hoechst 33342 dye and consequently produce a characteristic side population (SP) phenotype. ABCG2 (Human Breast Cancer Resistance Protein, BCRP) is the molecular determinant of the SP phenotype. We have demonstrated previously that the SP phenotype together with the expression of CD34 and lack of CD38 distinguishes between normal and leukemic stem cells in patients with acute myeloid leukemia (AML), suggesting a role of this protein in early human hematopoiesis. To test this, normal highly purified human CD34+ cord blood cells were transduced retrovirally by ABCG2/YFP and analyzed for their in vitro and in vivo behaviour. In vitro constitutive expression of ABCG2 doubled the number of the most immature CFU-GEMM type colonies in the CFC assays (n=12; p< 0.002). Furthermore, the protein enhanced the replating capacity of primary colonies with a mean 3.0 fold increase in the number of 2nd colonies (n=9; p< 0.01), indicating a substantial enhancement of the proliferative potential of clonogenic progenitors by constitutive ABCG2 expression. In contrast, ABCG2 did not induce any major increase in the frequency of LTC-IC compared to the YFP control after 5 days as assessed by limiting dilution LTC-IC (1 LTC-IC per 3911 cells and 1 LTC-IC per 3641 cells, respectively). To study the impact of ABCG2 on human progenitor cells in vivo NOD/SCID mice were injected with highly purified ABCG2/YFP+ cells and analyzed 8 weeks after transplantation for human engraftment. Although mice in the ABCG2 group received less transduced cells than the control (on average 1.2 x 105 versus 3.7 x 105 per mouse, respectively), they showed significant higher engraftment compared to the control group (6.1 x 107 transduced cells (4.3–8.2) versus 4.2 x 107 (3.2–5.7) per mouse, respectively; p<0.04). Mice that received ABCG2-transduced cells showed a 4.6fold increase in the number of engrafted CD34+ progenitor cells (1.4x 107 CD34+CD45+ vs 6.5x 106; p<0.05). In addition, ABCG2 expression resulted in 2.2-fold increase of c-KIT+ cells (6.1x106 cells vs. 2.8 x 106 cells in the control arm; p< 0.02) indicating that the constitutive expression of ABCG2 enhanced the number of human primitive progenitor cells. ABCG2 expression was also associated with an expansion in the CD15+ /CD33+ human myeloid compartment: in the control mice 1.1 x 107 human transduced myeloid cells (CD15+) were detected per mouse compared to 2.6 x 107 in the ABCG2 group 8 weeks post transplant (p<0.05) whereas the human CD19+ lymphoid compartment was not changed. This resulted in an inversion of the ratio of engrafted CD19+/CD15+ human lymphoid/myeloid cells (mean of 0.5 for ABCG2 vs 1.1 in the control; p<0.03). Furthermore, constitutive expression of ABCG2 promoted erythroid differentiation with a 3.6fold increase in glycophorin A expressing erythroid cells (9 x 106 vs 2.5 x 106 GlyA+ cells in the control; p < 0.003). Taken together, our data characterize ABCG2 as a previously unrecognized potent positive regulator of primitive hematopoietic cell growth in vitro and in vivo and extend our so far limited knowledge about human stem cell regulation by this ABC transporter.

Decreased PU.1 and Enhanced CITED2 Cooperate To Maintain Self-Renewal In Hematopoietic Stem/Progenitors

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2411-2411
Author(s):  
Hein Schepers ◽  
Patrick M. Korthuis ◽  
Jan Jacob Schuringa ◽  
Edo Vellenga
Keyword(s):  
Progenitor Cells ◽  
Conflicts Of Interest ◽  
Ectopic Expression ◽  
Fold Increase ◽  
Negative Regulator ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract The transcriptional co-activator CITED2 has a conserved role in the maintenance of normal adult hematopoiesis. We have shown before that CD34+ cells from a subset of acute myeloid leukemia (AML) patients display enhanced CITED2 expression and that interfering with this expression is detrimental for leukemia maintenance. Ectopic expression of CITED2 in normal CD34+ stem and progenitor cells (HSPCs) resulted in increased proliferation and skewed myelo-erythroid differentiation in vitro. Long-Term Culture-Initiating Cell assays (LTC-IC) revealed a 5-fold increase in the number of Cobblestone Area Forming Cells (CAFCs), as a result of an increase in the number of phenotypically defined CD34+CD38- HSCs. CFC frequencies were also enhanced 5-fold upon CITED2 overexpression. To further substantiate these observations in vivo, we transplanted CITED2-transduced CD34+ cells into NSG mice. CD34+ cells with increased CITED2 expression displayed a >10x higher engraftment at week 12, as compared to control cells, confirming the higher frequency of CD34+CD38- HSCs, while myelo-lymphoid differentiation of these cells was comparable to control transplanted cells. Till date we have not observed leukemia development in these transplanted mice, suggesting that CITED2 as a single hit is not sufficient to transform human CB CD34+ cells. We recently identified the myeloid transcription factor PU.1 as a strong negative regulator of CITED2 and enhanced CITED2 expression in AML samples correlates with low PU.1 expression. We therefore investigated whether high CITED2 and low PU.1 expression would collaborate in maintaining self-renewal of HSCs. We combined lentiviral downregulation of PU.1 with overexpression of CITED2 (PU.1Low-CITED2High) and performed LTC-IC cultures on MS5 stroma. These experiments revealed that combined loss of PU.1 and enhanced CITED2 expression was sufficient to induce a strong proliferative advantage compared to control cells. Furthermore, a 3-fold increase of progenitor numbers was observed in CFC assays. While overexpression of CITED2 alone was not sufficient to allow 2nd CFC formation, additional downregulation of PU.1 now led to colony formation upon serial replating. This replating capacity of PU.1Low-CITED2High cells was limited to CD34+CD38- HSCs, as replating of CD34+CD38+ progenitor cells did not yield CFCs. This suggests that the combined loss of PU.1 and enhanced CITED2 expression is sufficient to maintain self-renewal properties of HSC, but this combination is not sufficient to reinforce self-renewal in committed progenitor cells. To more stringently assess self-renewal, cells were first cultured for 4 weeks on MS5 under myeloid differentiating conditions (G-CSF, IL3 and TPO) and subsequently plated into CFC assays, followed by secondary and tertiary replating experiments. Only PU.1Low-CITED2High cells were able to form CFCs after 10 weeks of culture, indicating that this combination indeed preserves self-renewal. Current experiments focus on the in vivo engraftment and self-renewal properties of these PU.1Low-CITED2High cells. Preliminary data indicate that these PU.1Low-CITED2High cells contribute ∼3-fold more to the myeloid lineage at week 12, compared to control and CITED2 only cells, and AML development is currently being investigated in these mice. Together, these data suggest that CITED2 is sufficient to increase LTC-IC and CFC frequencies, to skew myeloid differentiation, and to enhance engraftment of CB CD34+ cells in xenograft mice. Furthermore, CITED2 overexpression together with reduced PU.1 levels is necessary to maintain stem cell self-renewal. Disclosures: No relevant conflicts of interest to declare.

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