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Series GSE121560 Query DataSets for GSE121560
Status Public on May 13, 2019
Title Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-seq of KLF6 KO)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML.
Overall design CRISPR-Cas9 mediated knockout of KLF6 was performed in human peripheral blood CD34+ cells (n=4 replicates). RNA-seq was utilized to determine the effect of KLF6 knockout compared to a non-targeting control control.
Contributor(s) Adelman ER, Huang H, Roisman A, Olsson A, Colaprico A, Qin T, Lindsley RC, Bejar R, Salomonis N, Grimes HL, Figueroa ME
Citation(s) 31085557
Submission date Oct 22, 2018
Last update date Aug 13, 2019
Contact name Maria E. Figueroa
Phone 305-243-7333
Organization name University of Miami Miller School Of Medicine
Department Human Genetics
Street address 1501 NW 10th Ave, BRB 742F
City Miami
State/province Florida
ZIP/Postal code 33136
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (8)
GSM3439213 AR005
GSM3439214 AR006
GSM3439215 AR007
This SubSeries is part of SuperSeries:
GSE104408 Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia
BioProject PRJNA497796
SRA SRP166275

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Supplementary file Size Download File type/resource
GSE121560_RAW.tar 1.8 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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