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Series GSE37000 Query DataSets for GSE37000
Status Public on Nov 01, 2012
Title The transcriptional landscape of hematopoietic stem cell ontogeny
Organism Mus musculus
Experiment type Expression profiling by array
Summary Transcriptome analysis of adult hematopoietic stem cells (HSC) and their progeny has informed our understanding of blood differentiation and leukemogenesis, but a similarly transformative analysis of the embryonic origins of hematopoiesis is lacking. To address this issue, we acquired gene expression profiles of developing HSC purified from over 2500 dissected murine embryos and adult mice, and applied a network biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs emerging from hemogenic endothelium, and definitive HSCs. We functionally validated several candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knock-down in zebrafish embryos, confirming changes in the expression of HSC markers runx1 and c-myb in the aorta-gonads-mesonephros (AGM), the site of definitive HSC specification. Moreover, we found that HSCs derived from differentiating embryonic stem cells in vitro (ESC-HSC) most closely resemble definitive HSC, yet lack a signature indicative of specification by Notch signaling, which likely accounts for their deficient lymphoid development. Our analysis and accompanying web resource will accelerate the characterization of regulators of HSC ontogeny, facilitate efforts to direct hematopoietic differentiation and cell fate conversion, and serve as a model to study the origins of other adult stem cells.
 
Overall design Hematopoietic stem cells and their precursors were isolated from mouse embryos and distinct stages and sites during development, purified by fluorescence activated cell sorting, and gene expression profiled on Affymetrix arrays. We also profiled HSCs and their precurors derived by in vitro differentitation of embryonic stem cells [expression data from GSE16925 and GSE14012 was used for mESCs, available at http://hsc.hms.harvard.edu/].
Web link http://hsc.hms.harvard.edu
 
Contributor(s) McKinney-Freeman S, Cahan P, Li H, Daley GQ
Citation(s) 23122293
Submission date Apr 03, 2012
Last update date Feb 11, 2019
Contact name Patrick Cahan
E-mail patrick.cahan@jhmi.edu
Organization name Johns Hopkins University School of Medicine
Department ICE and Biomedical Engineering
Lab Cahan Lab
Street address 733 North Broadway, MRB 653
City Baltimore
State/province MD
ZIP/Postal code 21205
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (47)
GSM908278 AGM_1
GSM908279 AGM_2
GSM908280 AGM_3
Relations
BioProject PRJNA157527

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
GSE37000_RAW.tar 159.5 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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