Iterative Single-Cell Analyses Define the Transcriptome of the First Functional Hematopoietic Stem Cells.

Abstract:

:Whereas hundreds of cells in the mouse embryonic aorta transdifferentiate to hematopoietic cells, only very few establish hematopoietic stem cell (HSC) identity at a single time point. The Gata2 transcription factor is essential for HSC generation and function. In contrast to surface-marker-based cell isolation, Gata2-based enrichment provides a direct link to the internal HSC regulatory network. Here, we use iterations of index-sorting of Gata2-expressing intra-aortic hematopoietic cluster (IAHC) cells, single-cell transcriptomics, and functional analyses to connect HSC identity to specific gene expression. Gata2-expressing IAHC cells separate into 5 major transcriptomic clusters. Iterative analyses reveal refined CD31, cKit, and CD27 phenotypic parameters that associate specific molecular profiles in one cluster with distinct HSC and multipotent progenitor function. Thus, by iterations of single-cell approaches, we identify the transcriptome of the first functional HSCs as they emerge in the mouse embryo and localize them to aortic clusters containing 1-2 cells.

journal_name

Cell Rep

journal_title

Cell reports

authors

Vink CS,Calero-Nieto FJ,Wang X,Maglitto A,Mariani SA,Jawaid W,Göttgens B,Dzierzak E

doi

10.1016/j.celrep.2020.107627

subject

Has Abstract

pub_date

2020-05-12 00:00:00

pages

107627

issue

6

issn

2211-1247

pii

S2211-1247(20)30580-5

journal_volume

31

pub_type

杂志文章
  • ABCE1 Controls Ribosome Recycling by an Asymmetric Dynamic Conformational Equilibrium.

    abstract::The twin-ATPase ABCE1 has a vital function in mRNA translation by recycling terminated or stalled ribosomes. As for other functionally distinct ATP-binding cassette (ABC) proteins, the mechanochemical coupling of ATP hydrolysis to conformational changes remains elusive. Here, we use an integrated biophysical approach ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.06.052

    authors: Gouridis G,Hetzert B,Kiosze-Becker K,de Boer M,Heinemann H,Nürenberg-Goloub E,Cordes T,Tampé R

    更新日期:2019-07-16 00:00:00

  • Brain States and Transitions: Insights from Computational Neuroscience.

    abstract::Within the field of computational neuroscience there are great expectations of finding new ways to rebalance the complex dynamic system of the human brain through controlled pharmacological or electromagnetic perturbation. Yet many obstacles remain between the ability to accurately predict how and where best to pertur...

    journal_title:Cell reports

    pub_type: 杂志文章,评审

    doi:10.1016/j.celrep.2020.108128

    authors: Kringelbach ML,Deco G

    更新日期:2020-09-08 00:00:00

  • Origin of Gamma Frequency Power during Hippocampal Sharp-Wave Ripples.

    abstract::Hippocampal sharp-wave ripples (SPW-Rs) support consolidation of recently acquired episodic memories and planning future actions by generating ordered neuronal sequences of previous or future experiences. SPW-Rs are characterized by several spectral components: a slow (5-15 Hz) sharp-wave, a high-frequency "ripple" os...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.10.066

    authors: Oliva A,Fernández-Ruiz A,Fermino de Oliveira E,Buzsáki G

    更新日期:2018-11-13 00:00:00

  • Interferon Gamma Mediates Hematopoietic Stem Cell Activation and Niche Relocalization through BST2.

    abstract::During chronic infection, the inflammatory cytokine interferon gamma (IFNγ) damages hematopoietic stem cells (HSCs) by disrupting quiescence and promoting excessive terminal differentiation. However, the mechanism by which IFNγ hinders HSC quiescence remains undefined. Using intravital 3-dimensional microscopy, we fin...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.108530

    authors: Florez MA,Matatall KA,Jeong Y,Ortinau L,Shafer PW,Lynch AM,Jaksik R,Kimmel M,Park D,King KY

    更新日期:2020-12-22 00:00:00

  • KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid Metabolism.

    abstract::The histone lysine demethylase KDM4C is often overexpressed in cancers primarily through gene amplification. The molecular mechanisms of KDM4C action in tumorigenesis are not well defined. Here, we report that KDM4C transcriptionally activates amino acid biosynthesis and transport, leading to a significant increase in...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.12.053

    authors: Zhao E,Ding J,Xia Y,Liu M,Ye B,Choi JH,Yan C,Dong Z,Huang S,Zha Y,Yang L,Cui H,Ding HF

    更新日期:2016-01-26 00:00:00

  • Molecular identification of t(w5): Vps52 promotes pluripotential cell differentiation through cell-cell interactions.

    abstract::After implantation, pluripotent epiblasts are converted to embryonic ectoderm through cell-cell interactions that significantly change the transcriptional and epigenetic networks. An entrée to understanding this vital developmental transition is the t(w5) mutation of the mouse t complex. This mutation produces highly ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2012.10.004

    authors: Sugimoto M,Kondo M,Hirose M,Suzuki M,Mekada K,Abe T,Kiyonari H,Ogura A,Takagi N,Artzt K,Abe K

    更新日期:2012-11-29 00:00:00

  • The Zinc Finger Transcription Factor Sp9 Is Required for the Development of Striatopallidal Projection Neurons.

    abstract::Striatal medium-sized spiny neurons (MSNs), composed of striatonigral and striatopallidal neurons, are derived from the lateral ganglionic eminence (LGE). We find that the transcription factor Sp9 is expressed in LGE progenitors that generate nearly all striatal MSNs and that Sp9 expression is maintained in postmitoti...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.06.090

    authors: Zhang Q,Zhang Y,Wang C,Xu Z,Liang Q,An L,Li J,Liu Z,You Y,He M,Mao Y,Chen B,Xiong ZQ,Rubenstein JL,Yang Z

    更新日期:2016-08-02 00:00:00

  • In Vivo Functional Mapping of a Cortical Column at Single-Neuron Resolution.

    abstract::The cerebral cortex is organized in vertical columns that contain neurons with similar functions. The cellular micro-architecture of such columns is an essential determinant of brain dynamics and cortical information processing. However, a detailed understanding of columns is incomplete, even in the best studied corti...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2019.04.007

    authors: Tischbirek CH,Noda T,Tohmi M,Birkner A,Nelken I,Konnerth A

    更新日期:2019-04-30 00:00:00

  • Functional genomic analysis of human mitochondrial RNA processing.

    abstract::Both strands of human mtDNA are transcribed in continuous, multigenic units that are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory chain biogenesis. We sought to systematically identify nuclear-encoded proteins that contribute to processing of mtRNAs within the organelle. First, we devised a...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.03.035

    authors: Wolf AR,Mootha VK

    更新日期:2014-05-08 00:00:00

  • Notch2 Signaling Maintains NSC Quiescence in the Murine Ventricular-Subventricular Zone.

    abstract::Neurogenesis continues in the ventricular-subventricular zone (V-SVZ) of the adult forebrain from quiescent neural stem cells (NSCs). V-SVZ NSCs are a reservoir for new olfactory bulb (OB) neurons that migrate through the rostral migratory stream (RMS). To generate neurons, V-SVZ NSCs need to activate and enter the ce...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.12.094

    authors: Engler A,Rolando C,Giachino C,Saotome I,Erni A,Brien C,Zhang R,Zimber-Strobl U,Radtke F,Artavanis-Tsakonas S,Louvi A,Taylor V

    更新日期:2018-01-23 00:00:00

  • KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response.

    abstract::The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlyin...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.03.079

    authors: Rabhi N,Denechaud PD,Gromada X,Hannou SA,Zhang H,Rashid T,Salas E,Durand E,Sand O,Bonnefond A,Yengo L,Chavey C,Bonner C,Kerr-Conte J,Abderrahmani A,Auwerx J,Fajas L,Froguel P,Annicotte JS

    更新日期:2016-05-03 00:00:00

  • The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.

    abstract::Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expre...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.08.075

    authors: Merienne N,Vachey G,de Longprez L,Meunier C,Zimmer V,Perriard G,Canales M,Mathias A,Herrgott L,Beltraminelli T,Maulet A,Dequesne T,Pythoud C,Rey M,Pellerin L,Brouillet E,Perrier AL,du Pasquier R,Déglon N

    更新日期:2017-09-19 00:00:00

  • Hybridization reveals the evolving genomic architecture of speciation.

    abstract::The rate at which genomes diverge during speciation is unknown, as are the physical dynamics of the process. Here, we compare full genome sequences of 32 butterflies, representing five species from a hybridizing Heliconius butterfly community, to examine genome-wide patterns of introgression and infer how divergence e...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2013.09.042

    authors: Kronforst MR,Hansen ME,Crawford NG,Gallant JR,Zhang W,Kulathinal RJ,Kapan DD,Mullen SP

    更新日期:2013-11-14 00:00:00

  • Severe Malaria Infections Impair Germinal Center Responses by Inhibiting T Follicular Helper Cell Differentiation.

    abstract::Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the es...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.12.006

    authors: Ryg-Cornejo V,Ioannidis LJ,Ly A,Chiu CY,Tellier J,Hill DL,Preston SP,Pellegrini M,Yu D,Nutt SL,Kallies A,Hansen DS

    更新日期:2016-01-05 00:00:00

  • Signaling Networks among Stem Cell Precursors, Transit-Amplifying Progenitors, and their Niche in Developing Hair Follicles.

    abstract::The hair follicle (HF) is a complex miniorgan that serves as an ideal model system to study stem cell (SC) interactions with the niche during growth and regeneration. Dermal papilla (DP) cells are required for SC activation during the adult hair cycle, but signal exchange between niche and SC precursors/transit-amplif...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.02.078

    authors: Rezza A,Wang Z,Sennett R,Qiao W,Wang D,Heitman N,Mok KW,Clavel C,Yi R,Zandstra P,Ma'ayan A,Rendl M

    更新日期:2016-03-29 00:00:00

  • LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex.

    abstract::Here, we ask how neural stem cells (NSCs) transition in the developing neocortex from a rapidly to a slowly proliferating state, a process required to maintain lifelong stem cell pools. We identify LRIG1, known to regulate receptor tyrosine kinase signaling in other cell types, as a negative regulator of cortical NSC ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.108257

    authors: Jeong D,Lozano Casasbuenas D,Gengatharan A,Edwards K,Saghatelyan A,Kaplan DR,Miller FD,Yuzwa SA

    更新日期:2020-10-13 00:00:00

  • Pten loss induces autocrine FGF signaling to promote skin tumorigenesis.

    abstract::Inactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.01.045

    authors: Hertzler-Schaefer K,Mathew G,Somani AK,Tholpady S,Kadakia MP,Chen Y,Spandau DF,Zhang X

    更新日期:2014-03-13 00:00:00

  • Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis.

    abstract::Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.01.051

    authors: Virk B,Jia J,Maynard CA,Raimundo A,Lefebvre J,Richards SA,Chetina N,Liang Y,Helliwell N,Cipinska M,Weinkove D

    更新日期:2016-02-23 00:00:00

  • Conservation of mRNA and protein expression during development of C. elegans.

    abstract::Spatiotemporal control of gene expression is crucial for development and subject to evolutionary changes. Although proteins are the final product of most genes, the developmental proteome of an animal has not yet been comprehensively defined, and the correlation between mRNA and protein abundance during development is...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2014.01.001

    authors: Grün D,Kirchner M,Thierfelder N,Stoeckius M,Selbach M,Rajewsky N

    更新日期:2014-02-13 00:00:00

  • A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts.

    abstract::The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance e...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.09.022

    authors: Nobis M,Herrmann D,Warren SC,Kadir S,Leung W,Killen M,Magenau A,Stevenson D,Lucas MC,Reischmann N,Vennin C,Conway JRW,Boulghourjian A,Zaratzian A,Law AM,Gallego-Ortega D,Ormandy CJ,Walters SN,Grey ST,Bailey J,Chta

    更新日期:2017-10-03 00:00:00

  • RNAi screening reveals proteasome- and Cullin3-dependent stages in vaccinia virus infection.

    abstract::A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection. Validation and analysis of clustered hits revealed previously unknown processes during virus entry, including a mechanism for genome uncoating. Viral core proteins were found to...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2012.09.003

    authors: Mercer J,Snijder B,Sacher R,Burkard C,Bleck CK,Stahlberg H,Pelkmans L,Helenius A

    更新日期:2012-10-25 00:00:00

  • Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder.

    abstract::Recent studies have established important roles of de novo mutations (DNMs) in autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and publis...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.12.074

    authors: Takata A,Miyake N,Tsurusaki Y,Fukai R,Miyatake S,Koshimizu E,Kushima I,Okada T,Morikawa M,Uno Y,Ishizuka K,Nakamura K,Tsujii M,Yoshikawa T,Toyota T,Okamoto N,Hiraki Y,Hashimoto R,Yasuda Y,Saitoh S,Ohashi K,Sakai

    更新日期:2018-01-16 00:00:00

  • The Anti-Warburg Effect Elicited by the cAMP-PGC1α Pathway Drives Differentiation of Glioblastoma Cells into Astrocytes.

    abstract::Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that ...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2016.12.037

    authors: Xing F,Luan Y,Cai J,Wu S,Mai J,Gu J,Zhang H,Li K,Lin Y,Xiao X,Liang J,Li Y,Chen W,Tan Y,Sheng L,Lu B,Lu W,Gao M,Qiu P,Su X,Yin W,Hu J,Chen Z,Sai K,Wang J,Chen F,Chen Y,Zhu S,Liu D,Cheng S,Xie Z

    更新日期:2017-01-10 00:00:00

  • Individual Control and Quantification of 3D Spheroids in a High-Density Microfluidic Droplet Array.

    abstract::As three-dimensional cell culture formats gain in popularity, there emerges a need for tools that produce vast amounts of data on individual cells within the spheroids or organoids. Here, we present a microfluidic platform that provides access to such data by parallelizing the manipulation of individual spheroids with...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.107670

    authors: Tomasi RF,Sart S,Champetier T,Baroud CN

    更新日期:2020-05-26 00:00:00

  • Cytoplasmic Control of Sense-Antisense mRNA Pairs.

    abstract::Transcriptome analyses have revealed that convergent gene transcription can produce many 3'-overlapping mRNAs in diverse organisms. Few studies have examined the fate of 3'-complementary mRNAs in double-stranded RNA-dependent nuclear phenomena, and nothing is known about the cytoplasmic destiny of 3'-overlapping messe...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.08.016

    authors: Sinturel F,Navickas A,Wery M,Descrimes M,Morillon A,Torchet C,Benard L

    更新日期:2015-09-22 00:00:00

  • Manipulation of Mitochondria Dynamics Reveals Separate Roles for Form and Function in Mitochondria Distribution.

    abstract::Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studie...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.04.017

    authors: Trevisan T,Pendin D,Montagna A,Bova S,Ghelli AM,Daga A

    更新日期:2018-05-08 00:00:00

  • Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.

    abstract::Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulat...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2015.08.039

    authors: Ino D,Sagara H,Suzuki J,Kanemaru K,Okubo Y,Iino M

    更新日期:2015-09-29 00:00:00

  • Psychedelics Promote Structural and Functional Neural Plasticity.

    abstract::Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine....

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2018.05.022

    authors: Ly C,Greb AC,Cameron LP,Wong JM,Barragan EV,Wilson PC,Burbach KF,Soltanzadeh Zarandi S,Sood A,Paddy MR,Duim WC,Dennis MY,McAllister AK,Ori-McKenney KM,Gray JA,Olson DE

    更新日期:2018-06-12 00:00:00

  • IDH1 Mutation Promotes Tumorigenesis by Inhibiting JNK Activation and Apoptosis Induced by Serum Starvation.

    abstract::Two hallmarks of cancer cells are their resistance to apoptosis and ability to thrive despite reduced levels of vital serum components. c-jun N-terminal kinase (JNK) activation is crucial for apoptosis triggered by serum starvation (SS), and isocitrate dehydrogenase 1 (IDH1) mutations are tumorigenic, in part, because...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2017.03.053

    authors: Jiang B,Zhang J,Xia J,Zhao W,Wu Y,Shi M,Luo L,Zhou H,Chen A,Ma H,Zhao Q,Suleman M,Lin F,Zhou L,Wang J,Zhang Y,He Y,Li X,Hung LM,Mak TW,Li Q

    更新日期:2017-04-11 00:00:00

  • Id1 and Id3 Maintain Steady-State Hematopoiesis by Promoting Sinusoidal Endothelial Cell Survival and Regeneration.

    abstract::Investigating mechanisms that regulate endothelial cell (EC) growth and survival is important for understanding EC homeostasis and how ECs maintain stem cell niches. We report here that targeted loss of Id genes in adult ECs results in dilated, leaky sinusoids and a pro-inflammatory state that increases in severity ov...

    journal_title:Cell reports

    pub_type: 杂志文章

    doi:10.1016/j.celrep.2020.107572

    authors: Gadomski S,Singh SK,Singh S,Sarkar T,Klarmann KD,Berenschot M,Seaman S,Jakubison B,Gudmundsson KO,Lockett S,Keller JR

    更新日期:2020-04-28 00:00:00