NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression

Starnes, Linda M.; Sorrentino, Antonio; Pelosi, Elvira; Ballarino, Monica; Morsilli, Ornella; Biffoni, Mauro; Santoro, Simona; Felli, Nadia; Castelli, Germana; Marchis, Maria Laura De; Mastroberardino, G; Gabbianelli, Marco; Fatica, Alessandro; Bozzoni, Irene; Nervi, Clara; Peschle, Cesare

doi:10.1182/blood-2008-12-196196

Cited by 56 publications

(67 citation statements)

References 47 publications

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“…Cases were classified according to the FrenchAmerican-British (FAB) classification and showed an initial percentage of circulating blasts Z80%. CD34 þ cells' collection, isolation, unilineage cultures and morphological analysis were performed as described 18,25,30,[45][46][47][48][49] according to institutional guidelines. For erythroid unilineage culture, the medium was supplemented with: human Epo (3 U/ml), interleukin-3 (IL-3; 0.01 U/ml) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.001 ng/ml).…”

Section: Aml Samples Cd34mentioning

confidence: 99%

“…Twenty-four hours after transfection, FITC-positive cells (3 Â 10 2 ) were suspended in 1 ml methylcellulose medium supplemented with SCF, GM-CSF, IL-3 and EPO 48 and plated in triplicate culture dishes. After 14 days incubation, each plate was scored for BFU-E, CFU-GM and CFU-GEMM growth.…”

Section: Aml Samples Cd34mentioning

confidence: 99%

“…Benzidine staining was performed as described. 18,30,48 The percentage of benzidine-positive cells (blue) was determined by light microscopic examination of at least 500 cells per sample. Morphology was evaluated in conventional light-field microscopy of Wright-Giemsa-stained cytospins.…”

Section: Aml Samples Cd34mentioning

confidence: 99%

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Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors

et al. 2013

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MicroRNAs (miRNAs) regulate cell proliferation, differentiation and death during development and postnatal life. The expression level of mature miRNAs results from complex molecular mechanisms, including the transcriptional regulation of their genes. MiR-223 is a hematopoietic-specific miRNA participating in regulatory signaling networks involving lineage-specific transcription factors (TFs). However, the transcriptional mechanisms governing its expression levels and its functional role in lineage fate decision of human hematopoietic progenitors (HPCs) have not yet been clarified. We found that in CD34þ HPCs undergoing unilineage differentiation/maturation, miR-223 is upregulated more than 10-fold during granulopoiesis, 3-fold during monocytopoiesis and maintained at low levels during erythropoiesis. Chromatin immunoprecipitation and promoter luciferase assays showed that the lineage-specific expression level of mature miR-223 is controlled by the coordinated binding of TFs to their DNA-responsive elements located in 'distal' and 'proximal' regulatory regions of the miR-223 gene, differentially regulating the transcription of two primary transcripts (pri-miRs). All this drives myeloid progenitor maturation into specific lineages. Accordingly, modulation of miR-223 activity in CD34þ HPCs and myeloid cell lines significantly affects their differentiation/ maturation into erythroid, granulocytic and monocytic/macrophagic lineages. MiR-223 overexpression increases granulopoiesis and impairs erythroid and monocytic/macrophagic differentiation. Its knockdown, meanwhile, impairs granulopoiesis and facilitates erythropoiesis and monocytic/macrophagic differentiation. Overall, our data reveal that transcriptional pathways acting on the differential regulation of two pri-miR transcripts results in the fine-tuning of a single mature miRNA expression level, which dictates the lineage fate decision of hematopoietic myeloid progenitors.

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Section: Aml Samples Cd34mentioning

confidence: 99%

Section: Aml Samples Cd34mentioning

confidence: 99%

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Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors

et al. 2013

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“…20 Recent studies suggest that NFI-A is a relevant target of the myeloid regulator miR-223 in promyelocytic leukemia cells as over-expression of NFIA suppresses monocytic and granulocytic differentiation of HPCs but accelerates erythropoiesis. 21,22 All these data suggest that NFIA is a crucial transcription factor involved in the differentiation of myeloid cells, especially granulocyte.…”

Section: 13mentioning

confidence: 96%

“…19 Meanwhile, NFIA acting as a crucial nuclear transcription factor has the ability to mediate lineage commitment and biology of myeloid cells. 21,22 Since NFIA expression in G-MDSCs was declined after WGP treatment, we hypothesized that NFIA may be related to the suppressive function of G-MDSCs. To determine a link between NFIA expression and the immunosuppression of G-MDSCs, GMDSCs isolated from spleen and tumor tissue were transfected with NFIA siRNA respectively to inhibit NFIA expression.…”

Section: Wgp Downregulates Expression Of Nfia In G-mdscs Via Dectin-1mentioning

confidence: 99%

Particulate β-glucan regulates the immunosuppression of granulocytic myeloid-derived suppressor cells by inhibiting NFIA expression

Tian

Tang

et al. 2015

OncoImmunology

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Pediatric Erythroid Sarcoma Diagnostically Confirmed by Identification of a Recurrent NFIA::CBFA2T3 Fusion

Anelo,

Ma,

Neary

et al. 2024

Genes Chromosomes & Cancer

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Erythroid sarcoma (ES) is exceedingly rare in the pediatric population with only a handful of reports of de novo cases, mostly occurring in the central nervous system (CNS) or orbit. It is clinically and pathologically challenging and can masquerade as a nonhematopoietic small round blue cell tumor. Clinical presentation of ES without bone marrow involvement makes diagnosis particularly difficult. We describe a 22‐month‐old female with ES who presented with a 2‐cm mass involving the left parotid region and CNS. The presence of crush/fixation artifact from the initial biopsy made definitive classification of this highly proliferative and malignant neoplasm challenging despite an extensive immunohistochemical workup. Molecular studies including RNA‐sequencing revealed a NFIA::CBFA2T3 fusion. This fusion has been identified in several cases of de novo acute erythroid leukemia (AEL) and gene expression analysis comparing this case to other AELs revealed a similar transcriptional profile. Given the diagnostically challenging nature of this tumor, clinical RNA‐sequencing was essential for establishing a diagnosis.

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NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls β-globin and G-CSF receptor expression

Cited by 56 publications

References 47 publications

Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors

Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors

Particulate β-glucan regulates the immunosuppression of granulocytic myeloid-derived suppressor cells by inhibiting NFIA expression

Pediatric Erythroid Sarcoma Diagnostically Confirmed by Identification of a Recurrent NFIA::CBFA2T3 Fusion

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