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Series GSE191029 Query DataSets for GSE191029
Status Public on May 15, 2023
Title Microenvironmental Control of Hematopoietic Niche Capacity via CXCL8 and Protein Kinase C
Organisms Danio rerio; Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling HSC fate are poorly understood. Genetically barcoded GESTALT zebrafish were used to screen for factors expressed by the sinusoidal vascular niche that alter the phylogenetic distribution of the HSC pool under native conditions. Dysregulated expression of protein kinase C delta (PKC-d, encoded by prkcda) increased the number of HSC clones by approximately 50% and expanded polyclonal populations of immature neutrophil and erythroid precursors. PKC agonists such as cxcl8 augmented HSC competition for residency within the niche and expanded defined niche populations. Cxcl8 induced association of PKC-d with the focal adhesion complex, activating MEK/ERK signaling and expression of niche factors in human endothelial cells. Our findings demonstrate the existence of reserve capacity within the niche which is controlled by PKC and has significant impact on HSC phylogenetic and phenotypic fate.
 
Overall design Single Cell RNA-seq and Single Cell ATAC-seq from zebrafish embryos and zebrafish kidney marrow. Bulk RNA-seq and bulk ATAC-seq from HUVEC cells transduced with adenovirus E4ORF1.
 
Contributor(s) Blaser BW
Citation(s) 37209097
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 DK128238 Epigenetic control of vascular niche capacity to support hematopoiesis. OHIO STATE UNIVERSITY Bradley Wayne Blaser
K08 DK111920 Regulation of zebrafish hematopoiesis by the sinusoidal endothelial cell niche OHIO STATE UNIVERSITY Bradley Wayne Blaser
Submission date Dec 16, 2021
Last update date Aug 14, 2023
Contact name Bradley Wayne Blaser
E-mail(s) bradley.blaser@osumc.edu
Organization name Ohio State University
Department Comprehensive Cancer Center
Lab Blaser Lab
Street address 400 W 12th Ave
City Columbus
State/province OH
ZIP/Postal code 43210
Country USA
 
Platforms (2)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
GPL24995 Illumina NovaSeq 6000 (Danio rerio)
Samples (21)
GSM5737703 1-runx-clover
GSM5737704 2-runx-cxcl8-2a-mcherry
GSM5737705 rosa_brad_aug2019_zf_4C
Relations
BioProject PRJNA789478

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE191029_RAW.tar 982.2 Mb (http)(custom) TAR (of BIGWIG, H5, NARROWPEAK, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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