NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE260462 Query DataSets for GSE260462
Status Public on May 29, 2024
Title Adult haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells and must respond to extracellular cues including cytokines.
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Adult haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood and immune cells and must respond to extracellular cues including cytokines. The JAK/STAT pathway is a highly conserved pathway, activated by many cytokines, in which tyrosine-phosphorylated STATs (pSTATs) function as transcription factors. STAT5 is a pivotal downstream mediator of several cytokines known to regulate haematopoiesis but its function in the HSC compartment remains poorly understood. Here we show that STAT5-deficient HSCs exhibited an unusual phenotype - reduced multi-lineage repopulation and self-renewal combined with reduced cell cycle entry and increased differentiation. This reflected not only loss of a canonical pSTAT5 transcriptional program but also loss of distinct functions mediated by tyrosine-unphosphorylated STAT5 (uSTAT5). Consistent with this concept expression of an unphosphorylatable STAT5B mutant constrained HSC differentiation, promoted HSC maintenance and upregulated transcriptional programs associated with quiescence and stemness. Moreover, treatment with a JAK1/2 inhibitor (ruxolitinib) increased the uSTAT5:pSTAT5 ratio, constrained HSC differentiation and proliferation and promoted HSC maintenance, thus phenocopying uSTAT5B overexpression. Our results therefore reveal a previously unrecognized interplay between pSTAT5 and uSTAT5 in the control of HSC function. In addition the demonstration that JAK inhibition promotes HSC maintenance has implications for gene therapy using HSCs and may contribute to the failure of JAK inhibitors to eradicate myeloproliferative neoplasms.
To evaluate the long-term functional capacity of uSTAT5B overexpressing HSCs, WT CD45.2 ESLAM HSCs were sorted and transduced with lentivirus containing STAT5B-YF, STAT5B-WT and EV in SCF and IL-11 cultures. Five days after infection, cells were sorted for viability (DAPI-, Thermo Fisher) and green fluorescent protein (GFP) expression and processed according to the manufacturer’s protocol for 10x Chromium (10x Genomics, Pleasanton, CA) experiments .
 
Overall design Matthew J Williams
 
Contributor(s) Wang X, Bastos HP, Wantoch M, Park HJ, Grondys-Kotarba G, Pask DC, Hamilton TL, Wilson NK, Kinston SJ, Asby R, Sneade R, Vassiliou GS, Laurenti E, Li J, Göttgens B, Green AR
Citation(s) 39374575
Submission date Feb 28, 2024
Last update date Jan 02, 2025
Contact name Xiaonan Wang
Organization name Shanghai Jiao Tong University School of Medicine
Department School of Public Health
Street address 227 Chongqing South Road
City Shanghai
ZIP/Postal code 200025
Country China
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM8117742 BM ESLAM HSCs, Rux 250nM, Mouse1
GSM8117743 BM ESLAM HSCs, DMSO, Mouse2
GSM8117744 BM ESLAM HSCs, Rux 250nM, Mouse2
Relations
BioProject PRJNA1081821

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

Supplementary file Size Download File type/resource
GSE260462_RAW.tar 123.7 Mb (http)(custom) TAR (of H5)
SRA Run SelectorHelp
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap