scholarly journals Coordinate expression and developmental role of Id2 protein and TAL1/E2A heterodimer in erythroid progenitor differentiation

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 164-175 ◽  
Author(s):  
G Condorelli ◽  
L Vitelli ◽  
M Valtieri ◽  
I Marta ◽  
E Montesoro ◽  
...  
Keyword(s):  
Cell Fate ◽  
Expression Pattern ◽  
Erythroid Differentiation ◽  
Hematopoietic Progenitor Cell ◽  
Rt Pcr ◽  
Mobility Shift ◽  
Erythroid Progenitor ◽  
Cell Fate Decisions ◽  
Coordinate Expression ◽  
Bhlh Genes

The Id proteins and basic helix-loop-helix (bHLH) proteins play major roles in specifying cell fate decisions in diverse biologic settings. A potential role for Id and TAL1/E2A bHLH genes in hematopoiesis has been suggested by studies on immortalized cell lines. However, it is uncertain whether these observations reflect normal hematopoiesis. We have investigated the expression pattern of Id2 and TAL1/E2A genes in liquid suspension culture of purified hematopoietic progenitor cell (HPCs) undergoing erythroid or granulopoietic differentiation in the first culture week and maturation to terminal cells in the second week. In quiescent, freshly purified HPCs, Id2 mRNA is detected by reverse transcriptase-polymerase chain reaction (RT-PCR), whereas TAL1 and E2A mRNAs are not. At the onset of erythroid differentiation, Id2 mRNA is downregulated, while E2A and TAL1 mRNAs are concomitantly upregulated: their expression is further increased at erythroblast level. Conversely, Id2 is not downmodulated in granulopoietic culture, except for a late decline at day 10 to 12, while TAL1 and E2A are only transiently induced in the first week of granulopoietic differentiation. The expression pattern of the TAL1/E2A heterodimer, as evaluated by mobility shift assay, is consistent with RT-PCR results (except for lower levels of the heterodimer in late erythroid maturation). TAL1 protein level, analyzed by Western blot, shows a pattern consistent with gelshift results. Functional experiments were performed on purified HPCs treated with phosphorothioate antisense oligodeoxynucleotides to Id2 or TAL1 mRNA. The results are strictly consistent with the expression studies: anti-Id2 oligomer (alpha-Id2) causes a significant dose-dependent increase of erythroid colony formation, whereas alpha-TAL1 induces a selective dose-related inhibitory effect on erythroid colonies, as compared with untreated or scrambled oligomer-treated control HPCs. Finally, murine and human glutathione-S-transferase (GST)-Id2 polypeptides compete the TAL1/E2A- specific DNA binding activity when added to the nuclear extracts derived from erythroid culture cells, thus indicating biochemical and suggesting functional interaction of Id2 with the TAL1/E2A complex. These novel observations indicate a coordinate expression and function of an inhibitory Id protein (Id2) and a stimulatory bHLH/bHLH heterodimer (TAL1/E2A) in normal erythroid differentiation.

scholarly journals Deletion of Mtg16, a Target of t(16;21), Alters Hematopoietic Progenitor Cell Proliferation and Lineage Allocation

2008 ◽  
Vol 28 (20) ◽  
pp. 6234-6247 ◽  
Author(s):  
Brenda J. Chyla ◽  
Isabel Moreno-Miralles ◽  
Melissa A. Steapleton ◽  
Mary Ann Thompson ◽  
Srividya Bhaskara ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Erythroid Progenitor ◽  
Cell Fate Decisions ◽  
Erythroid Progenitor Cells ◽  
Progenitor Cell Proliferation

ABSTRACT While a number of DNA binding transcription factors have been identified that control hematopoietic cell fate decisions, only a limited number of transcriptional corepressors (e.g., the retinoblastoma protein [pRB] and the nuclear hormone corepressor [N-CoR]) have been linked to these functions. Here, we show that the transcriptional corepressor Mtg16 (myeloid translocation gene on chromosome 16), which is targeted by t(16;21) in acute myeloid leukemia, is required for hematopoietic progenitor cell fate decisions and for early progenitor cell proliferation. Inactivation of Mtg16 skewed early myeloid progenitor cells toward the granulocytic/macrophage lineage while reducing the numbers of megakaryocyte-erythroid progenitor cells. In addition, inactivation of Mtg16 impaired the rapid expansion of short-term stem cells, multipotent progenitor cells, and megakaryocyte-erythroid progenitor cells that is required under hematopoietic stress/emergency. This impairment appears to be a failure to proliferate rather than an induction of cell death, as expression of c-Myc, but not Bcl2, complemented the Mtg16 − / − defect.

scholarly journals Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q− polycythemia vera

Blood ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 2812-2821 ◽  
Author(s):  
Fabiana Perna ◽  
Nadia Gurvich ◽  
Ruben Hoya-Arias ◽  
Omar Abdel-Wahab ◽  
Ross L. Levine ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Myeloproliferative Neoplasms ◽  
Erythroid Differentiation ◽  
Polycomb Group ◽  
Human Cord Blood ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Cd34 Cells

Abstract L3MBTL1, the human homolog of the Drosophila L(3)MBT polycomb group tumor suppressor gene, is located on chromosome 20q12, within the common deleted region identified in patients with 20q deletion-associated polycythemia vera, myelodysplastic syndrome, and acute myeloid leukemia. L3MBTL1 is expressed within hematopoietic CD34+ cells; thus, it may contribute to the pathogenesis of these disorders. To define its role in hematopoiesis, we knocked down L3MBTL1 expression in primary hematopoietic stem/progenitor (ie, CD34+) cells isolated from human cord blood (using short hairpin RNAs) and observed an enhanced commitment to and acceleration of erythroid differentiation. Consistent with this effect, overexpression of L3MBTL1 in primary hematopoietic CD34+ cells as well as in 20q− cell lines restricted erythroid differentiation. Furthermore, L3MBTL1 levels decrease during hemin-induced erythroid differentiation or erythropoietin exposure, suggesting a specific role for L3MBTL1 down-regulation in enforcing cell fate decisions toward the erythroid lineage. Indeed, L3MBTL1 knockdown enhanced the sensitivity of hematopoietic stem/progenitor cells to erythropoietin (Epo), with increased Epo-induced phosphorylation of STAT5, AKT, and MAPK as well as detectable phosphorylation in the absence of Epo. Our data suggest that haploinsufficiency of L3MBTL1 contributes to some (20q−) myeloproliferative neoplasms, especially polycythemia vera, by promoting erythroid differentiation.

scholarly journals Gfi1aa and Gfi1b set the pace for primitive erythroblast differentiation from hemangioblasts in the zebrafish embryo

2018 ◽  
Vol 2 (20) ◽  
pp. 2589-2606 ◽  
Author(s):  
Chris Moore ◽  
Joanna L. Richens ◽  
Yasmin Hough ◽  
Deniz Ucanok ◽  
Sunir Malla ◽  
...  
Keyword(s):  
Cell Fate ◽  
Fluorescent Protein ◽  
Erythroid Differentiation ◽  
Transcriptional Repressors ◽  
Rna Seq ◽  
Promote Cell Proliferation ◽  
Cell Fate Decisions ◽  
Maturation Defect ◽  
Green Fluorescent

Abstract The transcriptional repressors Gfi1(a) and Gfi1b are epigenetic regulators with unique and overlapping roles in hematopoiesis. In different contexts, Gfi1 and Gfi1b restrict or promote cell proliferation, prevent apoptosis, influence cell fate decisions, and are essential for terminal differentiation. Here, we show in primitive red blood cells (prRBCs) that they can also set the pace for cellular differentiation. In zebrafish, prRBCs express 2 of 3 zebrafish Gfi1/1b paralogs, Gfi1aa and Gfi1b. The recently identified zebrafish gfi1aa gene trap allele qmc551 drives erythroid green fluorescent protein (GFP) instead of Gfi1aa expression, yet homozygous carriers have normal prRBCs. prRBCs display a maturation defect only after splice morpholino-mediated knockdown of Gfi1b in gfi1aaqmc551 homozygous embryos. To study the transcriptome of the Gfi1aa/1b double-depleted cells, we performed an RNA-Seq experiment on GFP-positive prRBCs sorted from 20-hour-old embryos that were heterozygous or homozygous for gfi1aaqmc551, as well as wt or morphant for gfi1b. We subsequently confirmed and extended these data in whole-mount in situ hybridization experiments on newly generated single- and double-mutant embryos. Combined, the data showed that in the absence of Gfi1aa, the synchronously developing prRBCs were delayed in activating late erythroid differentiation, as they struggled to suppress early erythroid and endothelial transcription programs. The latter highlighted the bipotent nature of the progenitors from which prRBCs arise. In the absence of Gfi1aa, Gfi1b promoted erythroid differentiation as stepwise loss of wt gfi1b copies progressively delayed Gfi1aa-depleted prRBCs even further, showing that Gfi1aa and Gfi1b together set the pace for prRBC differentiation from hemangioblasts.

Identification of Alternative Splicing Changes in Erythroid Differentiation Using Human Exon Arrays.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1707-1707
Author(s):  
Miki L. Yamamoto ◽  
Jeong-Ah Kang ◽  
Josh A. Arribere ◽  
Amittha Wickrema ◽  
John G. Conboy
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Erythroid Differentiation ◽  
Transcriptional Level ◽  
Rt Pcr ◽  
Erythroid Progenitor ◽  
Array Data ◽  
Exon Arrays ◽  
Human Exon ◽  
A Genome

Abstract Terminal erythroid differentiation is accompanied by extensive structural remodeling as the cell enucleates and eventually assumes the biconcave disk morphology of the mature cell. Previous studies have documented many changes at the transcriptional level essential for erythroid differentiation. Changes in erythroid gene expression also occur at the level of pre-mRNA alternative splicing: the activation of 4.1R (EPB41) exon 16 splicing in late erythroblasts increases 4.1R affinity for spectrin-actin and mechanically strengthens the plasma membrane. We hypothesize that analogous changes in alternative splicing affect the structure and function of other erythroid proteins. To identify additional alternative splicing switches in erythroid genes, a genome-wide exon expression analysis was carried out using the new Affymetrix Human Exon 1.0 ST Array. Unlike traditional gene expression microarrays, this array has single exon resolution and can detect changes in expression due to alternative splicing. Samples for array analyses were prepared from RNA of human erythroid progenitor cells grown in culture for 7, 10, and 14 days, corresponding to basophilic, polychromatic, and orthochromatic stages. Analysis of this exon array data confirmed that 4.1R exon 16 splicing was activated in day 14 cells, and that a known inhibitor of exon 16 splicing, hnRNP A1, was down-regulated in coordination with the 4.1R splicing switch. As another positive control, we confirmed in array data the expression of a known erythroid-specific 3′ end in beta-spectrin mRNA in all three time points of erythroblasts, while array data from muscle tissue showed expression of only the non-erythroid 3′ end of beta-spectrin. Array data is now being analyzed to identify new cases of alternative splicing during erythropoiesis, and confirmation of several candidate splicing switches by RT-PCR and quantitative PCR is under way. A number of genes, including PIK3R1, SLC12A6, and TNPO2, show changes in alternative 5′ first exon usage during late erythropoiesis. A splicing change involving an internal cassette exon in MBNL2, which encodes a splicing regulator, was identified by array data and confirmed by RT-PCR. In addition, overall gene expression analyses confirm up-regulation of known genes expressed during erythroid differentiation, including Band 3, GLUT1, ALAS2, and BCL2L1. This preliminary analysis demonstrates the application of exon arrays toward the identification of splicing switches that occur during differentiation of human erythroblasts. Further validation of putative alternative splicing events is in progress, and investigation of the regulation of the validated events and the physiological implications of the predicted changes in the proteins will be pursued in the future.

Notch1-Induced Delay of Human Hematopoietic Progenitor Cell Differentiation Is Associated With Altered Cell Cycle Kinetics

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 838-848 ◽  
Author(s):  
Nadia Carlesso ◽  
Jon C. Aster ◽  
Jeffrey Sklar ◽  
David T. Scadden
Keyword(s):  
Cell Cycle ◽  
Cord Blood ◽  
Cell Fate ◽  
Active Form ◽  
Hematopoietic Progenitor Cell ◽  
Cell Phenotype ◽  
Cell Cycle Kinetics ◽  
Cell Fate Decisions ◽  
Cd34 Cells ◽  
Altered Cell

Hematopoiesis is a balance between proliferation and differentiation that may be modulated by environmental signals. Notch receptors and their ligands are highly conserved during evolution and have been shown to regulate cell fate decisions in multiple developmental systems. To assess whether Notch1 signaling may regulate human hematopoiesis to maintain cells in an immature state, we transduced a vesicular stomatitis virus G-protein (VSV-G) pseudo-typed bicistronic murine stem cell virus (MSCV)-based retroviral vector expressing a constitutively active form of Notch1 (ICN) and green fluorescence protein into the differentiation competent HL-60 cell line and primary cord blood–derived CD34+ cells. In addition, we observed endogenous Notch1 expression on the surface of both HL-60 cells and primary CD34+ cells, and therefore exposed cells to Notch ligand Jagged2, expressed on NIH3T3 cells. Both ligand-independent and ligand-dependent activation of Notch resulted in delayed acquisition of differentiation markers by HL-60 cells and cord blood CD34+ cells. In addition, primary CD34+cells retained their ability to form immature colonies, colony-forming unit–mix (CFU-mix), whereas control cells lost this capacity. Activation of Notch1 correlated with a decrease in the fraction of HL-60 cells that were in G0/G1phase before acquisition of a mature cell phenotype. This enhanced progression through G1 was noted despite preservation of the proliferative rate of the cells and the overall length of the cell cycle. These findings show that Notch1 activation delays human hematopoietic differentiation and suggest a link of Notch differentiation effects with altered cell cycle kinetics.

scholarly journals Blood Cell Fate Decisions: Insights from Single-cell RNA-seq

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-20-SCI-20
Author(s):  
Merav Socolovsky
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Cell Fate ◽  
Terminal Differentiation ◽  
S Phase ◽  
Erythroid Cell ◽  
Hematopoietic Progenitors ◽  
Erythroid Progenitor ◽  
Cell Fate Decisions ◽  
Computational Predictions

The manner by which multipotent hematopoietic progenitors commit to the erythroid lineage, and the subsequent processes that govern early erythroid progenitor development, are not well understood. Part of the challenge for investigating these was the lack of a rigorous strategy for isolating directly from tissue the early erythroid progenitors, which are functionally defined as the cell 'units' that give rise to erythroid colonies (CFU-e) or bursts (BFU-e) in culture. Indeed, the early erythroid trajectory, that starts with multi-potential progenitors and gives rise to BFU-e, CFU-e and to erythroblasts undergoing terminal differentiation, was not fully elucidated. We addressed these gaps using single cell transcriptomics, combined with functional assays that validated computational predictions 1. These showed that early hematopoietic progenitors form a continuous, hierarchical branching structure, in which the erythroid and basophil/mast cell fates are unexpectedly coupled. We delineated a novel flow-cytometric strategy that prospectively isolates CFU-e and BFU-e progenitors with high purity, and in combination with computational predictions, identified novel growth factor receptors that regulate early erythropoiesis. We further discovered that early erythroid development entails profound remodeling of both G1 and S phases of the cycle, resulting in cell cycle specializations that orchestrate the developmental process, including a gradual shortening of G1 during the CFU-e phase, followed by a sharp increase in the speed of S phase during the S-phase dependent activation of the erythroid terminal differentiation program 1-3(Figure 2). 1. Tusi BK, Wolock SL, Weinreb C, et al. Population snapshots predict early haematopoietic and erythroid hierarchies. Nature. 2018;555(7694):54-60. 2. Hwang Y, Futran M, Hidalgo D, et al. Global increase in replication fork speed during a p57KIP2-regulated erythroid cell fate switch. Science Advances. 2017;3:e1700298. 3. Pop R, Shearstone JR, Shen Q, et al. A key commitment step in erythropoiesis is synchronized with the cell cycle clock through mutual inhibition between PU.1 and S-phase progression. PLoS Biol. 2010;8(9). Disclosures No relevant conflicts of interest to declare.

Notch1 inhibits differentiation of hematopoietic cells by sustaining GATA-2 expression

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3283-3289 ◽  
Author(s):  
Keiki Kumano ◽  
Shigeru Chiba ◽  
Kiyoshi Shimizu ◽  
Tetsuya Yamagata ◽  
Noriko Hosoya ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Notch Signaling ◽  
Cell Fate ◽  
Hematopoietic Cells ◽  
Erythroid Differentiation ◽  
Inhibitory Effect ◽  
Dominant Negative ◽  
Granulocytic Differentiation ◽  
Cell Fate Decisions ◽  
Delayed Differentiation

Abstract Notch signaling is involved in cell fate decisions in many systems including hematopoiesis. It has been shown that expression of an activated form of Notch1 (aNotch1) in 32D mouse myeloid progenitor cells inhibits the granulocytic differentiation induced by granulocyte colony-stimulating factor (G-CSF). Results of the current study show that aNotch1, when expressed in F5-5 mouse erythroleukemia cells, also inhibits erythroid differentiation. Comparison of the expression levels of several transcription factors after stimulation for myeloid and erythroid differentiation, in the presence or absence of aNotch1, revealed that aNotch1 did not change its regulation pattern with any of the transcription factors examined, except for GATA-2, despite its inhibitory effect on differentiation. GATA-2 was down-regulated when the parental 32D and F5-5 were induced to differentiate into granulocytic and erythroid lineages, respectively. In these induction procedures, however, the level of GATA-2 expression was sustained when aNotch1 was expressed. To ascertain whether maintenance of GATA-2 is required for the Notch-induced inhibition of differentiation, the dominant-negative form of GATA-3 (DN-GATA), which acted also against GATA-2, or transcription factor PU.1, which was recently shown to be the repressor of GATA-2, was introduced into aNotch1-expressing 32D (32D/aNotch1) cells that do not express GATA family proteins other than GATA2. Both DN-GATA and PU.1 reversed the phenotype of 32D/aNotch1 inducing its differentiation when G-CSF was added. Furthermore, enforced expression of HES-1, which is involved in Notch signaling, delayed differentiation of 32D, and again this phenotype was neutralized by DN-GATA. These results indicate that GATA-2 activity is necessary for the Notch signaling in hematopoietic cells.

Constitutively active Notch4 promotes early human hematopoietic progenitor cell maintenance while inhibiting differentiation and causes lymphoid abnormalities in vivo

Blood ◽  
2004 ◽  
Vol 104 (8) ◽  
pp. 2315-2322 ◽  
Author(s):  
Suzanne M. Vercauteren ◽  
Heather J. Sutherland
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Cell Fate ◽  
Fluorescent Protein ◽  
Critical Role ◽  
Cell Activity ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Stem ◽  
Cell Fate Decisions ◽  
Constitutively Active

Abstract Notch transmembrane receptors are known to play a critical role in cell-fate decisions, with Notch1 shown to enhance self-renewal of hematopoietic stem cells and cause T-cell leukemia. Four Notch receptors exist, and the extent of redundancy and overlap in their function is unknown. Notch4 is structurally distinct from Notch1 through Notch3 and has not been extensively studied in hematopoiesis. By polymerase chain reaction (PCR) we find Notch4 transcript expression in human marrow cells and in both CD34+ and CD34– populations. When constitutively active Notch1 or Notch4 was overexpressed in normal human marrow or cord cells, we found reduced colony-forming and short-term proliferative ability while the primitive progenitor content of myeloid long-term cultures was significantly increased. Notch4–intracellular domain (Notch4-IC)–transduced cord cells transplanted into β2-microglobulin–/– nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in significantly higher levels of engraftment of both green fluorescent protein–positive (GFP+) and GFP– populations as compared with controls. GFP+ cells in bone marrow and spleen of animals that had received transplants gave rise to an immature CD4+CD8+ T-cell population, whereas B-cell development was blocked. These results indicate that activation of Notch4 results in enhanced stem cell activity, reduced differentiation, and altered lymphoid development, suggesting it may influence both stem cells and the fate of the common lymphoid progenitor.

scholarly journals Cell-specific transcriptional control of mitochondrial metabolism by TIF1γ drives erythropoiesis

Science ◽  
2021 ◽  
Vol 372 (6543) ◽  
pp. 716-721
Author(s):  
Marlies P. Rossmann ◽  
Karen Hoi ◽  
Victoria Chan ◽  
Brian J. Abraham ◽  
Song Yang ◽  
...  
Keyword(s):  
Cell Fate ◽  
Transcriptional Control ◽  
Cell Function ◽  
Coenzyme Q ◽  
Elongation Factor ◽  
Erythroid Differentiation ◽  
Mitochondrial Metabolism ◽  
Dihydroorotate Dehydrogenase ◽  
Functional Link ◽  
Cell Fate Decisions

Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. We discovered, using a chemical suppressor screen, that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1γ). This rescue depends on the functional link of DHODH to mitochondrial respiration. The transcription elongation factor TIF1γ directly controls coenzyme Q (CoQ) synthesis gene expression. Upon tif1γ loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon’s bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage.

scholarly journals Growth Factor Independence 1B-Mediated Transcriptional Repression and Lineage Allocation Require Lysine-Specific Demethylase 1-Dependent Recruitment of the BHC Complex

2019 ◽  
Vol 39 (13) ◽  
Author(s):  
David McClellan ◽  
Mattie J. Casey ◽  
Diana Bareyan ◽  
Helena Lucente ◽  
Christopher Ours ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Fate ◽  
Transcriptional Repression ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
Dependent Manner ◽  
Cell Fate Decisions ◽  
Lysine Specific Demethylase ◽  
Erythroleukemia Cells

ABSTRACTGrowth factor independence 1B (GFI1B) coordinates assembly of transcriptional repressor complexes comprised of corepressors and histone-modifying enzymes to control gene expression programs governing lineage allocation in hematopoiesis. Enforced expression of GFI1B in K562 erythroleukemia cells favors erythroid over megakaryocytic differentiation, providing a platform to define molecular determinants of binary fate decisions triggered by GFI1B. We deployed proteome-wide proximity labeling to identify factors whose inclusion in GFI1B complexes depends upon GFI1B’s obligate effector, lysine-specific demethylase 1 (LSD1). We show that GFI1B preferentially recruits core and putative elements of the BRAF-histone deacetylase (HDAC) (BHC) chromatin-remodeling complex (LSD1, RCOR1, HMG20A, HMG20B, HDAC1, HDAC2, PHF21A, GSE1, ZMYM2, and ZNF217) in an LSD1-dependent manner to control acquisition of erythroid traits by K562 cells. Among these elements, depletion of both HMG20A and HMG20B or of GSE1 blocks GFI1B-mediated erythroid differentiation, phenocopying impaired differentiation brought on by LSD1 depletion or disruption of GFI1B-LSD1 binding. These findings demonstrate the central role of the GFI1B-LSD1 interaction as a determinant of BHC complex recruitment to enable cell fate decisions driven by GFI1B.

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