Transcriptomics analysis of FAM122A knockout and NC K562 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE141735 | GEO | 2020/07/30
REPOSITORIES: GEO
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Project description:Transcriptomics analysis of FAM122A knockout and NC K562 cells
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Project description:We report differences in gene expression between WT and Fam122a KO LT-HSCs.
2020-05-28 | GSE151261 | GEO
Project description:While effective anti-cancer drugs targeting the CHK1 kinase are advancing in the clinic, drug resistance is rapidly emerging. Here, we demonstrate that CRISPR-mediated knockout of the little-known gene FAM122A confers cellular resistance to CHK1 inhibitors and cross-resistance to ATR inhibitors. Knockout of FAM122A results in activation of PP2A-B55α, a phosphatase which dephosphorylates the WEE1 protein and rescues WEE1 from Ubiquitin-mediated degradation. The resulting increase in WEE1 protein expression reduces replication stress, activates the G2/M checkpoint, and confers cellular resistance to CHK1 inhibitors. Interestingly, in tumor cells with oncogene-driven replication stress, CHK1 can directly phosphorylate FAM122A, leading to activation of the PP2A-B55α phosphatase and increased WEE1 expression. A combination of a CHK1 inhibitor plus a WEE1 inhibitor can overcome CHK1 inhibitor resistance of these tumor cells, thereby enhancing anti-cancer activity. The FAM122A expression level in a tumor cell can serve as a useful biomarker for predicting CHK1 inhibitor sensitivity or resistance.
2021-01-01 | GSE158338 | GEO
Project description:Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved house-keeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multi facet physiological and pathological processes, however, the in vivo function of FAM122A is largely unknown. In this study, we found that Fam122 deletion results in embryonic lethality with severe defects of cardiovascular developments and significantly attenuates the cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impairs mesendodermal specification and cardiac differentiation from mouse embryonic stem cells, but not influences the pluripotent identity. Mechanical investigation shows that the impaired differentiation potential is caused through the dysregulation of histone modification and Wnt and Hippo signaling pathways by modulating PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This not only significantly extends our understanding the regulatory network of mesendodermal/cardiac differentiation, but also establishes a previously uncharacterized connection between PP2A and mesendodermal specification.
2022-08-18 | GSE211235 | GEO
Project description:Mesendodermal specification and cardiac differentiation are key issues for developmental biology and heart regeneration medicine. Previously, we demonstrated that FAM122A, a highly conserved house-keeping gene, is an endogenous inhibitor of protein phosphatase 2A (PP2A) and participates in multi facet physiological and pathological processes, however, the in vivo function of FAM122A is largely unknown. In this study, we found that Fam122 deletion results in embryonic lethality with severe defects of cardiovascular developments and significantly attenuates the cardiac functions in conditional cardiac-specific knockout mice. More importantly, Fam122a deficiency impairs mesendodermal specification and cardiac differentiation from mouse embryonic stem cells, but not influences the pluripotent identity. Mechanical investigation shows that the impaired differentiation potential is caused through the dysregulation of histone modification and Wnt and Hippo signaling pathways by modulating PP2A activity. These findings suggest that FAM122A is a novel and critical regulator in mesendodermal specification and cardiac differentiation. This not only significantly extends our understanding the regulatory network of mesendodermal/cardiac differentiation, but also establishes a previously uncharacterized connection between PP2A and mesendodermal specification.
2022-08-18 | GSE211234 | GEO
Project description:We previously characterized zinc finger protein gene HZF1 (ZNF16) and demonstrated its important roles in erythroid and megakaryocytic differentiation of K562 cells by loss-function assay. However its effect in erythroid and megakaryocytic differentiation of hematopoietic stem/progenitor cells (HSPCs) and the mechanisms by which it functions have not been understood. In this study, we detected up-regulation of ZNF16 during erythroid and megakaryocytic differentiation of K562 cells and normal CD34+ HSPCs, and demonstrated that ZNF16 promotes erythroid and megakaryocytic differentiation by gain-of-function and loss-of-function experiments. Gene expression profiling by mRNA array and PCR validation in the K562 transforments with ZNF16 over-expression suggested that cell division cycle-associated 7-like gene (JPO2) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog gene (c-KIT) were among the genes regulated possibly by ZNF16. Luciferase reporter assay and Chromatin Immunoprecipitation demonstrated that ZNF16 binds to JPO2 and c-KIT promoters and inhibits their expression in K562 cells. A significant decrease of JPO2 and c-KIT levels was observed during erythroid and megakaryocytic differentiation of K562 and CD34+ cells. The knockdown of either JPO2 or c-KIT partially rescued the differentiation inhibition caused by ZNF16 knockdown. We also found that ZNF16 inhibits c-KIT/c-Raf/MEK/ERK/c-Jun/HEY1 signal pathways, which finally up-regulated expression of GATA1, a central regulator of erthroid and megakaryocyte differentiation. By lentivirus-mediated gene transfer, we demonstrated that enforced expression and knockdown of ZNF16 in HSPCs down-regulated and up-regulated expression of its targets respectively. Our data collectively demonstrate that ZNF16 promotes erythropoiesis and megakaryocytopoiesis via its regulation on JPO2 and c-KIT. 4 samples are analyzed, H4-1 and H4-2 are two stable K562 transductants with ZNF16 over-expression, PC1 and PC2 are stable control K562 transductants. Stable K562 transductants were obtained for RNA extraction and hybridization on an Illumina HumanHT-12 V4.0 expression beadchipe xpression Array platform.
2016-03-29 | E-GEOD-46593 | biostudies-arrayexpress
Project description:Expresssion data in K562 cells, before and after TPA induction and including a RUNX1 knockout construct or a control structure Examination of gene expression in K562 cells, before and following TPA induction and with or without a RUNX1 KO construct or control
2011-01-10 | E-GEOD-24778 | biostudies-arrayexpress
Project description:Homeobox genes encode transcription factors that control patterning of virtually all organ systems including the hematopoietic system. However, the role of homeobox genes in controlling development of the erythroid and megakaryocytic lineages is poorly understood. In this study, we investigated the role of the homeobox gene DLX4 in erythroid and megakaryocytic differentiation using the bipotent cell line K562 as a model. We compared the global gene expression profile of K562 cells that stably overexpressed DLX4 with that of vector-control K562 cells. As positive controls, global gene expression profiles were evaluated in vector-control K562 cells that were stimulated with Activin A (ActA) to induce erythroid differentiation and in vector-control K562 cells that were stimulated with phorbol 12-myristate 13-acetate (PMA) to induce megakaryocytic differentiation. Our study provides insights into the role of homeobox genes in controlling differentiation of the erythroid and megakaryocytic lineages. Three groups of samples were included: DLX4 vs Empty vector; Activin A vs None; PMA vs DMSO
2015-09-02 | E-GEOD-63888 | biostudies-arrayexpress
Project description:PML functions as a platform for the interaction of transcription factors and coactivators. Role of PML in erythroid clone formation has been reported but the detail mechanism is unclear. We used microarrays to identify downstream-regulated genes of PML4. We transfected K562 cells with retrovirus overexpressing PML4 and control vector pMSCV for RNA extraction and hybridization on Affymetrix microarrays.
2013-07-13 | E-GEOD-48842 | biostudies-arrayexpress
Project description:Identification of Fam122a regulated genes in LT-HSCs.
| PRJNA635351 | ENA