ArrayExpress Uploader0mouseC57BL/6Nugenaorta-gonads-mesonephrosembryonic day 11.5VE-cadherin+CD45+Specifyingin vivoC57BL/6Nugenaorta-gonads-mesonephrosembryonic day 11.5VE-cadherin+CD45+Specifyingin vivoC57BL/6Nugenaorta-gonads-mesonephrosembryonic day 11.5VE-cadherin+CD45+Specifyingin vivoC57BL/6Nugenaorta-gonads-mesonephrosembryonic day 11.5VE-cadherin+CD45+Specifyingin vivoC57BL/6Nugenaorta-gonads-mesonephrosembryonic day 11.5VE-cadherin+CD45+Specifyingin vivoC57BL/6Nugenaorta-gonads-mesonephrosembryonic day 11.5VE-cadherin+CD45+Specifyingin vivoC57BL/6 x 129 crossNugennot specifieddifferentiation day 6c-kit+CD41+YS-likein vitroC57BL/6 x 129 crossNugennot specifieddifferentiation day 6c-kit+CD41+YS-likein vitroC57BL/6 x 129 crossnannot specifieddifferentiation day 6c-kit+CD41+YS-likein vitroC57BL/6 x 129 crossNugennot specifieddifferentiation day 6c-kit+CD41+YS-likein vitroC57BL/6 x 129 crossnannot specifieddifferentiation day 6c-kit+CD41+YS-likein vitroC57BL/6 x 129 crossNugennot specifieddifferentiation day 6c-kit+CD41+YS-likein vitroC57BL/6 x 129 crossnannot specifieddifferentiation day 10-14CD41brightCD45-CD34-Definitivein vitroC57BL/6 x 129 crossnannot specifieddifferentiation day 10-14CD41brightCD45-CD34-Definitivein vitroC57BL/6 x 129 crossnannot specifieddifferentiation day 10-14CD41brightCD45-CD34-Definitivein vitroC57BL/6Nugenfetal liverembryonic day 12.5Lin-Sca-1+c-kit+VE-cadherin+Mac-1lowDefinitivein vivoC57BL/6Nugenfetal liverembryonic day 12.5Lin-Sca-1+c-kit+VE-cadherin+Mac-1lowSpecifyingin vivoC57BL/6Nugenfetal liverembryonic day 12.5Lin-Sca-1+c-kit+VE-cadherin+Mac-1lowSpecifyingin vivoC57BL/6Nugenfetal liverembryonic day 12.5Lin-Sca-1+c-kit+VE-cadherin+Mac-1lowDefinitivein vivoC57BL/6Nugenfetal liverembryonic day 12.5Lin-Sca-1+c-kit+VE-cadherin+Mac-1lowDefinitivein vivoC57BL/6Nugenfetal liverembryonic day 12.5Lin-Sca-1+c-kit+VE-cadherin+Mac-1lowDefinitivein vivoC57BL/6Nugenfetal liverembryonic day 13.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6Nugenfetal liverembryonic day 13.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6Nugenfetal liverembryonic day 13.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6Nugenfetal liverembryonic day 13.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6nanfetal liverembryonic day 14.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6Nugenfetal liverembryonic day 14.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6nanfetal liverembryonic day 14.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6Nugenfetal liverembryonic day 14.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6nanfetal liverembryonic day 14.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6Nugenfetal liverembryonic day 14.5Lin-Sca-1+c-kit+CD150+CD48-Definitivein vivoC57BL/6nanplacentaembryonic day 12.5CD45+CD34medc-kit+Specifyingin vivoC57BL/6nanplacentaembryonic day 12.5CD45+CD34medc-kit+Specifyingin vivoC57BL/6nanplacentaembryonic day 12.5CD45+CD34medc-kit+Specifyingin vivoC57BL/6Nugenplacentaembryonic day 12.5CD45+CD34medc-kit+Specifyingin vivoC57BL/6Nugenplacentaembryonic day 12.5CD45+CD34medc-kit+Specifyingin vivoC57BL/6Nugenplacentaembryonic day 12.5CD45+CD34medc-kit+Specifyingin vivoC57BL/6nanbone marrowadultLin-Sca-1+c-kit+CD150+CD34-Definitivein vivoC57BL/6Nugenbone marrowadultLin-Sca-1+c-kit+CD150+CD34-Definitivein vivoC57BL/6Nugenbone marrowadultLin-Sca-1+c-kit+CD150+CD34-Definitivein vivoC57BL/6nanbone marrowadultLin-Sca-1+c-kit+CD150+CD34-Definitivein vivoC57BL/6Nugenbone marrowadultLin-Sca-1+c-kit+CD150+CD34-Definitivein vivoC57BL/6nanyolk sacembryonic day 9CD41+CD34+c-kit+YS-likein vivoC57BL/6nanyolk sacembryonic day 9CD41+CD34+c-kit+YS-likein vivoC57BL/6nanyolk sacembryonic day 9CD41+CD34+c-kit+YS-likein vivoC57BL/6Nugenyolk sacembryonic day 9CD41+CD34+c-kit+YS-likein vivoC57BL/6Nugenyolk sacembryonic day 9CD41+CD34+c-kit+YS-likein vivo6837arrayexpress_sid6[u'Transcriptome analysis of adult hematopoietic stem cells (HSC) and their progeny has informed our understanding of blood...E-GEOD-37000/profile/8773/arrayexpressuploader747aortacellendotheliummesonephrosnotchyolk sacDec.12, 2014Falsethe-transcriptional-landscape-of-hematopoietic-steE-GEOD-37000_A-AFFY-45The transcriptional landscape of hematopoietic stem cell ontogenyNov.12, 2014[u'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. 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 ', {u'a': {u'href': u'http://hsc.hms.harvard.edu/', u'target': u'_blank', u'$': u'http://hsc.hms.harvard.edu/'}}, u'].']http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-37000http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-37000/samples/