van Oudenaarden: Quantitative biology

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The Van Oudenaarden group uses a combination of experimental, computational, and theoretical approaches to quantitatively understand decision‐making in single cells, with a focus on questions in developmental and stem cell biology.

We are particularly interested in how cells use gene networks to make robust decisions even in the presence of significant fluctuations in gene expression. We use and develop a wide range of single-cell methods including single-cell sequencing and quantitative imaging tools.

Key publicationsView all publications

High-throughput total RNA sequencing in single cells using VASA-seq

F. Salmen, J. De Jonghe, T.S. Kaminski, A. Alemany, G.E. Parada, J. Verity-Legg, Ayaka Yanagida, T.N. Kohler, N. Battich, F. van den Brekel, A.L. Ellermann, A. Martinez Arias, J. Nichols, M. Hemberg, F. Hollfelder, A. van Oudenaarden

Nature Biotechnology (online ahead of print)


Integration of multiple lineage measurements from the same cell reconstructs parallel tumor evolution

L. Kester, B. de Barbanson, A. Lyubimova, L.T. Chen, V. van der Schrier, A. Alemany, D. Mooijman, J. Peterson-Maduro, J. Drost, J. de Ridder, A. van Oudenaarden

Cell Genomics 2, 100096


Single-cell Ribo-seq reveals cell cycle-dependent translational pausing

M. VanInsberghe, J. van den Berg, A. Andersson-Rolf, H. Clevers, A. van Oudenaarden

Nature 597, 561-565


An in vitro model of early anteroposterior organization during human development

N. Moris, K. Anlas, S. C. van den Brink, A. Alemany, J. Schröder, S. Ghimire, T. Balayo, A. van Oudenaarden and A. Martinez Arias

Nature 582, 410-415


Sequencing metabolically labeled transcripts in single cells reveals mRNA turnover strategies

N. Battich, J. Beumer, B. de Barbanson, L. Krenning, C. S. Baron, M. E. Tanenbaum, H. Clevers and A. van Oudenaarden

Science 367, 1151–1156


Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids

S. C. van den Brink, A. Alemany, V. van Batenburg, N. Moris, M. Blotenburg, J. Vivié, P. Baillie-Johnson, J. Nichols, K. F. Sonnen, A. Martinez Arias and A. van Oudenaarden

Nature 582, 405-409


Nature Reviews Molecular Cell Biology 20, 753-765


Cell type purification by single-cell transcriptome-trained sorting

C. S. Baron, A. Barve, M. J. Muraro, R. van der Linden, G. Dharmadhikari, A. Lyubimova, E. J. P. de Koning, and A. van Oudenaarden

Cell 179, 527 - 542


Mapping the physical network of cellular interactions

J. C. Boisset, J. Vivié, D. Grün, M. J. Muraro, A. Lyubimova, and A. van Oudenaarden

Nature Methods 15, 547 - 553


Single-cell transcriptomics meets lineage tracing

L. Kester and A. van Oudenaarden

Cell Stem Cell 23, 166-179


Whole-organism clone tracing using single-cell sequencing

A. Alemany, M. Florescu, C. S. Baron, J. Peterson-Maduro, and A. van Oudenaarden

Nature 556, 108 – 112


Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations

S. C. van den Brink, F. Sage, Á. Vértesy, B. Spanjaard, J. Peterson-Maduro, C. S. Baron, C. Robin, and A. van Oudenaarden

Nature Methods 14, 935 – 936


De novo prediction of stem cell identity using single-cell transcriptome data

D. Grün, M. J. Muraro, J. C. Boisset, K. Wiebrands, A. Lyubimova, G. Dharmadhikari, M. van den Born, J. van Es, E. Jansen, H. Clevers, E.J.P. de Koning, and A. van Oudenaarden

Cell Stem Cell 19, 266 – 277


A single-cell transcriptome atlas of the human pancreas

M. J. Muraro, G. Dharmadhikari, D. Grün, N. Groen, T. Dielen, E. Jansen, L. van Gurp, M. A. Engelse, F. Carlotti, E.J.P. de Koning, and A. van Oudenaarden

Cell Systems 3, 385 – 394


Single-cell 5hmC sequencing reveals chromosome-wide cell-to-cell variability and enables lineage reconstruction

D. Mooijman, S. S. Dey, J. C. Boisset, N. Crosetto, and A. van Oudenaarden

Nature Biotechnology 34, 852 – 856


Single-cell mRNA sequencing reveals rare intestinal cell types

D. Grün, A. Lyubimova, L. Kester, K. Wiebrands, O. Basak, N. Sasaki, H. Clevers, and A. van Oudenaarden

Nature 525, 251 – 255


Integrated genome and transcriptome sequencing of the same cell

S. S. Dey, L. Kester, B. Spanjaard, M. Bienko, and A. van Oudenaarden

Nature Biotechnology 33, 285 – 289


Cell 163, 799 – 810


MicroRNA control of protein expression noise

J. M. Schmiedel, S. L. Klemm, Y. Zheng, A. Sahay, N. Blüthgen, D. S. Marks, and A. van Oudenaarden

Science 348, 128 – 132


Genome-wide RNA tomography in the zebrafish embryo

J. P. Junker, E. S. Noel, V. Guryev, K. A. Peterson, G. Shah, J. Huisken, A. P. McMahon, E. J. Berezikov, J. Bakkers, and A. van Oudenaarden

Cell 159, 662 – 675


Other publications

Trends Cell Biology 9, 747-759


Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development

M. Sen, D. Mooijman, A. Chialastri, J.C. Boisset, M. Popovic, B. Heindryckx, S.M. Chuva de Sousa Lopes , S.S. Dey, A. van Oudenaarden

Nature Communications 12, 1286


Parental haplotype-specific single-cell transcriptomics reveal incomplete epigenetic reprogramming in human female germ cells

Á. Vértesy, W. Arindrarto, M. S. Roost, B. Reinius, V. Torrens-Juaneda, M. Bialecka, I. Moustakas, Y. Ariyurek, E. Kuijk, H. Mei, R. Sandberg, A. van Oudenaarden, and S. M. Chuva de Sousa Lopes

Nature Communications 9, 1873


Blastocyst-like structures generated solely from stem cells

N. C. Rivron, J. Frias-Aldeguer, E. Vrij, J. C. Boisset, J. Korving, J. Vivié, R. Truckenmüller, A. van Oudenaarden, C. A. van Blitterswijk, and N. Geijsen

Nature 557, 106 - 111


Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

S. Semrau, J. E. Goldmann, M. Soumillon, T. S. Mikkelsen, R. Jaenisch, and A. van Oudenaarden

Nature Communications 8: 1096


Identity and dynamics of mammary stem cells during branching morphogenesis

C. L. Scheele, E. Hannezo, M. J. Muraro, A. Zomer, N. S. Langedijk, A. van Oudenaarden, B. D. Simons, and J. van Rheenen

Nature 542, 313-317


Cell Stem Cell 20, 177-190


Replacement of lost Lgr5-positive stem cells through plasticity of their enterocyte-lineage daughters

P. W. Tetteh, O. Basak, H. F. Farin, K. Wiebrands, K. Kretzschmar, H. Begthel, M. van den Born, J. Korving, F. de Sauvage, J. H. van Es, A. van Oudenaarden, and H. Clevers

Cell Stem Cell 18, 203 – 213


Dissecting immune circuits by linking CRISPR-pooled screens with single-cell RNA-seq

D. A. Jaitin, A. Weiner, I. Yofe, D. Lara-Astiaso, H. Keren-Shaul, E. David, T. M. Salame, A. Tanay, A. van Oudenaarden, and I. Amit

Cell 167, 1883-1896


Plasticity between epithelial and mesenchymal states unlinks EMT from metastasis-enhancing stem cell capacity

E. Beerling, D. Seinstra, E. de Wit, L. Kester, D. van der Velden, C. Maynard, R. Schäfer, P. van Diest, E. Voest, A. van Oudenaarden, N. Vrisekoop, and J. van Rheenen

Cell Reports 14, 2281 – 2288


Spatially resolved genome-wide transcriptional profiling identifies BMP signaling as essential regulator of zebrafish cardiomyocyte regeneration

C. C. Wu, F. Kruse, M. D. Vasudevarao, J. P. Junker, D. C. Zebrowski, K. Fischer, E. S. Noël, D. Grün, E. Berezikov, F. B. Engel, A. van Oudenaarden, G. Weidinger, and J. Bakkers

Developmental Cell 36, 36 – 49


Annual Review of Cell and Developmental Biology 31, 317 – 345


Differential stoichiometry among core ribosomal proteins

N. Slavov, S. Semrau, E. Airoldi, B. Budnik, and A. van Oudenaarden

Cell Reports 13, 865 – 873


Ascl2 acts as a R-spondin/Wnt-responsive switch to control stemness in intestinal crypt

J. Schuijers, J. P. Junker, M. Mokry, P. Hatzis, B. K. Koo, V. Sasselli, L. G. van der Flier, E. Cuppen, A. van Oudenaarden, and H. Clevers

Cell Stem Cell 16, 158 – 170


Genome-wide maps of nuclear lamina interactions in single human cells

J. Kind, L. Pagie, S. S. de Vries, L. Nahidiazar, S. S. Dey, M. Bienko, Y. Zhan, B. Lajoie, C. A. de Graaf, M. Amendola, G. Fudenberg, M. Imakaev, L. A. Mirny, K. Jalink, J. Dekker, A. van Oudenaarden, and B. van Steensel

Cell 63, 134 – 147


Cells change their sensitivity to an EGF morphogen gradient to control EGF-induced gene expression

J. S. van Zon, S. Kienle, G. Huelsz-Prince, M. Barkoulas, and A. van Oudenaarden

Nature Communications 6: 7053


Validation of noise models for single-cell transcriptomics

D. Grün, L. Kester, and A. van Oudenaarden

Nature Methods 11, 637 – 640


A predictive model of bifunctional transcription factor signaling during embryonic tissue patterning

J. P. Junker, K. A. Peterson, Y. Nishi, J. Mao, A. P. McMahon, and A. van Oudenaarden

Developmental Cell 31, 448 – 460


Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans

R. A. Mentink, T. C. Middelkoop L. Rella, N. Ji, C. Y. Tang, M. C. Betist, A. van Oudenaarden, and H. C. Korswagen

Developmental Cell 31, 188 – 201


Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma

A. Barreca, C. Martinengo, L. Annaratone, L. Righi, A. Chiappella, M. Ladetto, A. Demurtas, L. Chiusa, A. Stacchini, N. Crosetto, A. van Oudenaarden, and R. Chiarle

Blood Cancer Journal Oct 10; 4:e249


Constant growth rate can be supported by decreasing energy flux and increasing aerobic glycolysis

N. Slavov, B. A. Budnik, D. Schwab, E. M. Airoldi, and A. van Oudenaarden

Cell Reports 7, 705 – 714


Transcriptional profiling of cells sorted by RNA abundance

S. Klemm, S. Semrau, K. Wiebrands, D. Mooijman, D. A. Faddah, R. Jaenisch, and A. van Oudenaarden

Nature Methods 11, 549 – 551


Cell 157, 8 – 11


Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

V. Almendro, Y. K. Cheng, A. Randles, S. Itzkovitz, A. Marusyk, E. Ametller, X. Gonzalez-Farre, M. Muñoz, H. G. Russnes, A. Helland, I. H. Rye, A. L. Borresen-Dale, R. Maruyama, A. van Oudenaarden, M. Dowsett, R. L. Jones, J. Reis-Filho, P. Gascon, M. Gönen, F. Michor, and K. Polyak

Cell Reports 6, 514 – 527


Genetic and Phenotypic Diversity in Breast Tumor Metastases

V. Almendro, H. J. Kim, Y. K. Cheng, M. Gönen, S. Itzkovitz, P. Argani, A. van Oudenaarden, S. Sukumar, F. Michor, and K. Polyak

Cancer Research 74, 1 – 11


Global discovery of erythroid long non-coding RNAs reveals novel regulators of red cell maturation

J. R. Alvarez-Dominguez, W. Hu, B. Yuan, J. Shi , S. S. Park, A. A. Gromatzk, A. van Oudenaarden, and H. F. Lodish

Blood 123, 570 – 581


FuseFISH: Robust detection of transcribed gene fusions in single cells

S. Semrau, N. Crosetto, M. Bienko, M. Boni, P. Bernasconi, R. Chiarle, and A. van Oudenaarden

Cell Reports 6, 18 – 23


Proceedings of the National Academy of Sciences USA 110, 18602 – 18607


Feedback control of gene expression variability in the Caenorhabditis elegans Wnt pathway

N. Ji, T. C. Middelkoop, R. A. Mentink, M. C. Betist, S. Tonegawa, D. Mooijman, H. C. Korswagen, and A. van Oudenaarden

Cell 155, 869 – 880


Nature Genetics 45, 1337 – 1344


Single-molecule mRNA detection and counting in mammalian tissue

A. Lyubimova, S. Itzkovitz, J. P. Junker, Z. P. Fan, X. Wu, and A. van Oudenaarden

Nature Protocols 8, 1743 – 1758


Nature Methods 10, 869 – 871


Stochastic cytokine expression induces mixed T helper cell states

M. Fang, H. Xie, S. K. Dougan, H. Ploegh, and A. van Oudenaarden

PLoS Biology 11: e1001618


Systematic identification of signal-activated stochastic gene regulation

G. Neuert, B. Munsky, R. Z. Tan, L. Teytelman, M. Khammash, and A. van Oudenaarden

Science 339, 584-587


Robustness and epistasis in the C. elegans vulval signaling network revealed by pathway dosage modulation

M. Barkoulas, J. S. van Zon, J. Milloz, A. van Oudenaarden, and M. A. Félix

Developmental Cell 24, 64-75


Deconvolving the roles of Wnt ligands and receptors in sensing and amplification

R. Z. Tan, N. Ji, R. A. Mentink, H. C. Korswagen, and A. van Oudenaarden

Molecular Systems Biology 9:631


A versatile genome-scale PCR-based pipeline for high-definition DNA FISH

M. Bienko, N. Crosetto, L. Teytelman, S. Klemm, S. Itzkovitz, and A. van Oudenaarden

Nature Methods 10, 122-124


Cell Stem Cell 11, 452-460


Using gene expression noise to understand gene regulation

B. Munsky, G. Neuert, and A. van Oudenaarden

Science 336, 183-187


Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase

Y. Buganim, D. A. Faddah, A. W. Cheng, E. Itskovich, S. Markoulaki, K. Ganz, S. L. Klemm, A. van Oudenaarden, and R. Jaenisch

Cell 150, 1209-1212


Slug and sox9 cooperatively determine the mammary stem cell state

W. Guo, Z. Keckesova, J. L. Donaher, T. Shibue, V. Tischler, F. Reinhardt, S. Itzkovitz, A. Noske, U. Zürrer-Härdi, G. Bell, W. L. Tam, S. A. Mani, A. van Oudenaarden, and R. A. Weinberg

Cell 148, 1015-1028


Single-cell analysis reveals that noncoding RNAs contribute to clonal heterogeneity by modulating transcription factor recruitment

S. Bumgarner, G. Neuert, B. F. Voight, A. Symbor-Nagrabska, P. Grisafi, A. van Oudenaarden, and G. R. Fink

Molecular Cell 45, 470-482


Single-molecule transcript counting of stem-cell markers in the mouse intestine

S. Itzkovitz, A. Lyubimova, I.C. Blat, M. Maynard, J. van Es, J. Lees, T. Jacks, H. Clevers, A. van Oudenaarden

Nature Cell Biology 14, 106-114


Optimality in development of intestinal crypts

S. Itzkovitz, I. Blat, T. Jacks, H. Clevers, and A. van Oudenaarden

Cell 148, 608-619


Validating transcripts with probes and imaging technology

S. Itzkovitz and A. van Oudenaarden

Nature Methods 8, S12-S19


MicroRNAs can generate thresholds in target gene expression

S. Mukherji, M.S. Ebert, G. X. Y. Zheng, J.S. Tsang, P.A. Sharp, and A. van Oudenaarden

Nature Genetics 43, 854-859


Cellular decision-making and biological noise: from microbes to mammals

G. Balázsi, A. van Oudenaarden, and J.J. Collins

Cell 144, 910-925


A general mechanism for network-dosage compensation in gene networks

M. Acar, B.F. Pando, F.H. Arnold, M.B. Elowitz, and A. van Oudenaarden

Science 329, 1656-1660


Molecular Cell 38, 140-153


Circadian gating of the cell cycle revealed in single cyanobacterial cells

Q. Yang, B. F. Pando, G. Dong, S. S. Golden, and A. van Oudenaarden

Science 327, 1522-1526


Variability in gene expression underlies incomplete penetrance

A. Raj, S.A. Rifkin, E. Andersen, and A. van Oudenaarden

Nature 463, 913-918


Nature Review Genetics 10, 859-871


Nature 462, 875-880


A systems-level analysis of perfect adaptation in yeast osmoregulation

D. Muzzey, C. Gomez-Uribe, J.T. Mettetal, and A. van Oudenaarden

Cell 138, 160-171


Snowdrift game dynamics and facultative cheating in yeast

J. Gore, H. Youk, and A. van Oudenaarden

Nature 459, 253-256


Cell 135, 216-226


Imaging individual mRNA molecules using multiple singly labeled probes

A. Raj, P. van den Bogaard, S.A. Rifkin, A. van Oudenaarden, and S. Tyagi

Nature Methods 5, 877-879


Stochastic switching as a survival strategy in fluctuating environments

M. Acar, J.T. Mettetal, and A. van Oudenaarden

Nature Genetics 40, 471-475


The frequency dependence of osmo-adaptation in Saccharomyces cerevisiae

J.T. Mettetal, D. Muzzey, C. Gomez-Uribe, and A. van Oudenaarden

Science 319, 482-484


Stochastic gene expression out-of-steady-state in the cyanobacterial circadian clock

J.R. Chabot, J.M. Pedraza, P. Luitel, and A. van Oudenaarden

Nature 450, 1249-1252


Nature Genetics 39, 269-275


Molecular Cell 26, 753-767


Enhancement of cellular memory by reducing stochastic transitions

M. Acar, A. Becskei, and A. van Oudenaarden

Nature 435, 228


Noise propagation in gene networks

J.M. Pedraza and A. van Oudenaarden

Science 307, 1965-1969


Nature Genetics 37, 937-944


Multistability in the lactose utilization network of Escherichia coli

E.M. Ozbudak, M. Thattai, H.N. Lim, B.I. Shraiman, and A. van Oudenaarden

Nature 427, 737


Amplitude control of cell-cycle waves by nuclear import

A. Becskei, M.G. Boselli, and A. van Oudenaarden

Nature Cell Biology 6, 451


Regulation of noise in the expression of a single gene

E. Ozbudak, M. Thattai, I. Kurtser, A.D. Grossman and A. van Oudenaarden

Nature Genetics 31, 69


Intrinsic noise in gene regulatory networks

M. Thattai and A. van Oudenaarden

PNAS 98, 8614


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Group leader

Alexander van Oudenaarden

Alexander van Oudenaarden is group leader at the Hubrecht Institute and professor of quantitative biology of gene regulation at the University Medical Center Utrecht and Utrecht University. The Van Oudenaarden group combines biology with physics and informatics to gain insight in the quantitative biology of development and stem cells. They develop new techniques to quantify gene expression and study the regulation of gene expression in single cells. Alexander van Oudenaarden is one of the pioneers of single cell RNA-sequencing and his lab has developed several bio-informatics tools to analyze these data in detail. Their main interest is to investigate the mechanisms by which cells with the same genotype and identical growth environment develop different phenotypes.

Scientific training and positions


Current other activities

Group members

Alexander van Oudenaarden

Group Leader

Josi Peterson


Reinier van der Linden


Anna van Oudenaarden

Senior Researcher

Peter Zeller


Michael Vaninsberghe


Vivek Bhardwaj


Jeroen van den Berg


Max Wellenstein


Amir Giladi


Cansu Koyunlar


Soufiane Mourragui


Chih-Yao Chung


Marloes Blotenburg

PhD Student

Helena Viñas Gaza

PhD Student

Joe Verity-Legg

PhD Student

Vincent van Batenburg

PhD Student

Nune Schelling

PhD Student

Björn van Sambeek

PhD Student

Eugenio Marinelli

PhD Student

Alberto Griffa

PhD Student

Eirini Daskalaki


Bert Jan Korte


Floris Leenders


Joshua Peterson


Chiara Baggio


Widad Mammer Bouhou


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Alumni – Postdoctoral Students

Alumni – Graduate Students