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RNA Sequencing Facilitates Quantitative Analysis of Wild Type and MEIS1 deleted H1 drived cells at day6 of megakaryocytic differentiation

ABSTRACT: Purpose: The goals of this study are to investigate the molecular mechanism by which MEIS1 controls megakaryocytic maturation and thrombopoiesis through compareing the mRNA profiling of Wild Type and MEIS1 deleted H1 drived cells at day6 of megakaryocytic differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE92244 | GEO | 2018/01/31

REPOSITORIES: GEO

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RNA Sequencing Facilitates Quantitative Analysis of Wild Type and MEIS1 deleted H1 drived cells at day3 of hematopoietic differentiation

Project description:Purpose: The goals of this study are to investigate the molecular mechanism by which MEIS1 controls HEP specification through compareing the mRNA profiling of Wild Type and MEIS1 deleted H1 drived cells at day3 of hematopoietic differentiation. Conclusions:a large number of genes were down-regulated in MEIS1-deleted H1 hESCs when compared with the wild-type cells. Among those, a number of mammalian hematopoiesis-associated genes such as FLI1, APLN, TAL1 and MYB were significantly down-regulated.

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Project description:Purpose: The goals of this study are to investigate the molecular mechanism by which MEIS2 controls HEP specification and EHT through compareing the mRNA profiling of Wild Type and MEIS2 deleted H1 drived cells at day4 of hematopoietic differentiation. Methods: mRNA profiles of Wild Type and MEIS2 deleted H1 drived cells at day4 of hematopoietic differentiation were generated by deep sequencing using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using TaqMan and SYBR Green assays Conclusions:a large number of genes were down-regulated in MEIS2-deleted H1 hESCs when compared with the wild-type cells. Among those, a number of mammalian hematopoiesis-associated genes such as TAL1 ,GFI and GATA2 were significantly down-regulated.

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Project description:RNA Sequencing Facilitates Quantitative Analysis of Wild Type and MEIS1 deleted H1 drived cells at day6 of megakaryocytic differentiation

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Project description:The transcription factor Meis1 is preferentially expressed in hematopoietic stem cells (HSCs) and over-expressed in certain leukemias. However, the functions of Meis1 in hematopoiesis remain largely unknown. Using inducible knock-out mice, we found that Meis1 is required for the maintenance of hematopoiesis under stress and over long term while steady-state hematopoiesis was sustained in the absence of Meis1. Bone marrow cells of Meis1 deficient mice showed reduced colony formation, contained significantly fewer numbers of long- term HSCs and these Meis1-deficient HSCs exhibited loss of quiescence. Further, we found that Meis1 deletion led to the accumulation of reactive oxygen species (ROS) in HSCs and decreased expression of genes implicated in hypoxia response. Finally, ROS scavenging by N-acetyl cysteine or stabilization of hypoxia-signaling by knockdown of the VHL protein led to reversal of the effects of Meis1-deletion. Taken together, these results demonstrate that Meis1 protects and preserves HSCs by restricting oxidative metabolism.

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