Deletion of the Prdm3 Gene Causes a Neuronal Differentiation Deficiency in P19 Cells

Leszczyński, Paweł; Śmiech, Magdalena; Teeli, Aamir Salam; Haque, Effi; Viger, Robert S.; Ogawa, Hidesato; Pierzchała, Mariusz; Taniguchi, Hiroaki

doi:10.3390/ijms21197192

Cited by 6 publications

(5 citation statements)

References 56 publications

(74 reference statements)

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“…However, the neuronal-specific role of PRDM3 remains to be addressed in mammals, and PRDM3 could be implicated in the onset of neurogenesis. Recently, our study showed that P19 cells with Prdm3 gene knock-out displayed earlier maturation of neurons along with the rapid proliferation of non-neuronal cells [102]. These findings strongly showed the significant role of PRDM3 in the formation of the mammalian nervous system in vivo.…”

Section: The Function Of Prdm3 and Prdm16 In Neuronal Cellssupporting

confidence: 52%

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Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors)

Leszczyński

Śmiech

Parvanov

et al. 2020

Cells

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PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1) (PR) homologous domain containing (PRDM) transcription factors are expressed in neuronal and stem cell systems, and they exert multiple functions in a spatiotemporal manner. Therefore, it is believed that PRDM factors cooperate with a number of protein partners to regulate a critical set of genes required for maintenance of stem cell self-renewal and differentiation through genetic and epigenetic mechanisms. In this review, we summarize recent findings about the expression of PRDM factors and function in stem cell and neuronal systems with a focus on cofactor-dependent regulation of PRDM3/16 and FOG1/2. We put special attention on summarizing the effects of the PRDM proteins interaction with chromatin modulators (NuRD complex and CtBPs) on the stem cell characteristic and neuronal differentiation. Although PRDM factors are known to possess intrinsic enzyme activity, our literature analysis suggests that cofactor-dependent regulation of PRDM3/16 and FOG1/2 is also one of the important mechanisms to orchestrate bidirectional target gene regulation. Therefore, determining stem cell and neuronal-specific cofactors will help better understanding of PRDM3/16 and FOG1/2-controlled stem cell maintenance and neuronal differentiation. Finally, we discuss the clinical aspect of these PRDM factors in different diseases including cancer. Overall, this review will help further sharpen our knowledge of the function of the PRDM3/16 and FOG1/2 with hopes to open new research fields related to these factors in stem cell biology and neuroscience.

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Section: The Function Of Prdm3 and Prdm16 In Neuronal Cellssupporting

confidence: 52%

“…Gene knock-out leads to precocious neuronal differentiation in the P19 cells (direct mechanism unknown, increased expression of MAP2 and β-III TUBULIN). [102] Hamlet (Drosophila melanogaster PRDM3 and PRDM16 homolog) removes notch-dependent fate signature during neuronal-class diversification via direct chromatin-modification.…”

Section: Prdm3/evi1mentioning

confidence: 99%

Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors)

Leszczyński

Śmiech

Parvanov

et al. 2020

Cells

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“…Like Neuro2a cells, ACSF2 had a Golgi specific localization in mouse P19 teratocarcinoma cells, as indicated by colocalization with Golgin 97 (Fig. 5A-C); both Neuro2a cells and P19 cells have been studied as models for neurogenesis [24]. In contrast to Neuro2a and P19 cells, however, mouse MA10 (testicular Leydig) cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

ACSF2: A MEDIUM-CHAIN ACYL-CoA SYNTHETASE WITH A POTENTIAL ROLE IN NEURONAL DIFFERENTIATION

Maiguel

Morita

Pei

et al. 2022

Preprint

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By activating fatty acids to their CoA derivatives, acyl CoA synthetases (ACS) play an essential role in fatty acid metabolism. We previously identified ACSF2 as an ACS that was phylogenetically distinct from known families of short-chain, medium-chain, long-chain, very long-chain, and bubblegum ACSs. Functionally, ACSF2 preferentially activated medium-chain fatty acids. In this work, we provide further characterization of this unique ACS. ACSF2 mRNA expression was found in most tissues, although immunohistochemical analysis revealed differences in protein expression between various cell types in each tissue. Endogenous ACSF2 was found in the Golgi region in Neuro2a and P19 cells, and disruption of the Golgi in Neuro2a cells with nocodazole disrupted ACSF2 localization. In contrast, MA-10, HepG2, and skin fibroblasts had a mitochondrial ACSF2 localization. ACSF2 activated saturated fatty acids containing 6 to 10 carbons when overexpressed in COS-1 cells. The Kmapp for C10:0 was 24.4 mM and Vmaxapp was 385 nmol/20min/mg COS cell protein. Knockdown by RNA interference revealed that ACSF2 was responsible for most of the medium-chain ACS activity in Neuro2a cells. A lysine residue critical for activity in bacterial short-chain ACSs was found in ACSF2, and mutation of this residue to alanine abolished enzyme activity. Neurite outgrowth results when Neuro2a cells are induced to differentiate with retinoic acid, and ACSF2 migrated to nodes and points of neurite-neurite contact along with the presynaptic marker, synaptophysin. ACSF2 deficient Neuro2a cells showed significantly blunted neurite outgrowth in response to retinoic acid. These results suggest that this medium-chain ACS may play an important role in neuronal development.

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“…The ATTO-550 ribonucleoprotein CRISPR cas9 (RNP) complex was combined with Lipofectamine® CRISPRMAX™ (Thermo Fisher Scientific, Inc.) by incubation at 4°C for 30 min, and the mixture was subsequently used for transfection. A highly efficient procedure ( 30 ) was followed precisely for the transfection experiments.…”

Section: Methodsmentioning

confidence: 99%

FABP5 can substitute for androgen receptor in malignant progression of prostate cancer cells

Naeem,

Abdulsamad,

Zeng

et al. 2023

Int J Oncol

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Fatty acid-binding protein 5 (FABP5) and androgen receptor (AR) are critical promoters of prostate cancer. In the present study, the effects of knocking out the FABP5 or AR genes on malignant characteristics of prostate cancer cells were investigated, and changes in the expression of certain key proteins in the FABP5 (or AR)-peroxisome proliferator activated receptor-γ (PPARγ)-vascular endothelial growth factor (VEGF) signaling pathway were monitored. The results obtained showed that FABP5 - or AR -knockout (KO) led to a marked suppression of the malignant characteristics of the cells, in part, through disrupting this signaling pathway. Moreover, FABP5 and AR are able to interact with each other to regulate this pathway, with FABP5 controlling the dominant AR splicing variant 7 (ARV7), and AR, in return, regulates the expression of FABP5. Comparisons of the RNA profiles revealed the existence of numerous differentially expressed genes (DEGs) comparing between the parental and the FABP5 - or AR -KO cells. The six most abundant changes in DEGs were found to be attributable to the transition from androgen-responsive to androgen-unresponsive, castration-resistant prostate cancer (CRPC) cells. These findings have provided novel insights into the complex molecular pathogenesis of CRPC cells, and have demonstrated that interactions between FABP5 and AR contribute to the transition of prostate cancer cells to an androgen-independent state. Moreover, gene enrichment analysis revealed that the most highly enriched biological processes associated with the DEGs included those responsive to fatty acids, cholesterol and sterol biosynthesis, as well as to lipid and fatty acid transportation. Since these pathways regulated by FABP5 or AR may be crucial in terms of transducing signals for cancer cell progression, targeting FABP5, AR and their associated pathways, rather than AR alone, may provide a new avenue for the development of therapeutic strategies geared towards suppressing the malignant progression to CRPC cells.

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Deletion of the Prdm3 Gene Causes a Neuronal Differentiation Deficiency in P19 Cells

Cited by 6 publications

References 56 publications

Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors)

Emerging Roles of PRDM Factors in Stem Cells and Neuronal System: Cofactor Dependent Regulation of PRDM3/16 and FOG1/2 (Novel PRDM Factors)

ACSF2: A MEDIUM-CHAIN ACYL-CoA SYNTHETASE WITH A POTENTIAL ROLE IN NEURONAL DIFFERENTIATION

FABP5 can substitute for androgen receptor in malignant progression of prostate cancer cells

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