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

Quantifying DNA replication speeds in single cells by scEdU-seq

J. van den Berg, V. van Batenburg, , C. Geisenberger, R.B. Tjeerdsma, A. de Jaime-Soguero, S.P. Acebrón, M.A.T. M. van Vugt, A. van Oudenaarden 

Nature Methods 21, 1175–1184 (2024).

Download|2024

scChIX-seq infers dynamic relationships between histone modifications in single cells

J. Yeung, M. Florescu, P. Zeller, B.A. de Barbanson, M.D. Wellenstein, A. van Oudenaarden

Nature Biotechnology 41, 813-823

Download|2023

Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis

P. Zeller, J. Yeung, H. Viñas Gaza, B.A. de Barbanson, V. Bhardwaj, M. Florescu, R. van der Linden, A. van Oudenaarden

Nature Genetics 55, 333-345

Download|2023

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 40, 1780-1793

Download|2022

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

Download|2022

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

Download|2021

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

Download|2020

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

Download|2020

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

Download|2020

Nature Reviews Molecular Cell Biology 20, 753-765

Download|2019

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

Download|2019

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

Download|2018

Single-cell transcriptomics meets lineage tracing

L. Kester and A. van Oudenaarden

Cell Stem Cell 23, 166-179

Download|2018

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

Download|2018

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

Download|2017

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

Download|2016

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

Download|2016

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

Download|2016

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

Download|2015

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

Download|2015

Cell 163, 799 – 810

Download|2015

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

Download|2015

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

Download|2014

Other publications

Trends Cell Biology 31, 747-759

Download|202109

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

Download|20210224

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

Download|20181004

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

Download|20180504

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

Download|20170201

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

Download|20170201

Cell Stem Cell 20, 177-190

Download|20170201

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

Download|20160201

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

Download|20160204

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

Download|20160205

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

Download|20160201

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

Download|20150201

Differential stoichiometry among core ribosomal proteins

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

Cell Reports 13, 865 – 873

Download|20150201

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

Download|20150201

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

Download|20150201

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

Download|20150201

Validation of noise models for single-cell transcriptomics

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

Nature Methods 11, 637 – 640

Download|20141122

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

Download|20140401

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

Download|20140401

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

Download|20140404

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

Download|20140401

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

Download|20140401

Cell 157, 8 – 11

Download|20140401

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

Download|20140402

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

Download|20140401

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

Download|20140402

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

Download|20140401

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

Download|20130401

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

Download|20130401

Nature Genetics 45, 1337 – 1344

Download|20130401

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

Download|20130401

Nature Methods 10, 869 – 871

Download|20130401

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

Download|20130401

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

Download|20130401

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

Download|20130401

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

Download|20130404

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

Download|20130401

Cell Stem Cell 11, 452-460

Download|20120401

Using gene expression noise to understand gene regulation

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

Science 336, 183-187

Download|20120406

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

Download|20120401

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

Download|20120405

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

Download|20120401

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

Download|20120401

Optimality in development of intestinal crypts

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

Cell 148, 608-619

Download|20120401

Validating transcripts with probes and imaging technology

S. Itzkovitz and A. van Oudenaarden

Nature Methods 8, S12-S19

Download|20110401

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

Download|20110401

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

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

Cell 144, 910-925

Download|20110401

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

Download|20100402

Molecular Cell 38, 140-153

Download|20100401

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

Download|20100401

Variability in gene expression underlies incomplete penetrance

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

Nature 463, 913-918

Download|20100401

Nature Review Genetics 10, 859-871

Download|20090401

Nature 462, 875-880

Download|20090401

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

Download|20090401

Snowdrift game dynamics and facultative cheating in yeast

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

Nature 459, 253-256

Download|20090401

Cell 135, 216-226

Download|20080401

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

Download|20080401

Stochastic switching as a survival strategy in fluctuating environments

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

Nature Genetics 40, 471-475

Download|20080401

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

Download|20080401

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

Download|20070501

Nature Genetics 39, 269-275

Download|20070501

Molecular Cell 26, 753-767

Download|20070501

Enhancement of cellular memory by reducing stochastic transitions

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

Nature 435, 228

Download|20050501

Noise propagation in gene networks

J.M. Pedraza and A. van Oudenaarden

Science 307, 1965-1969

Download|20050501

Nature Genetics 37, 937-944

Download|20050501

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

Download|20040501

Amplitude control of cell-cycle waves by nuclear import

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

Nature Cell Biology 6, 451

Download|20040501

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

Download|20020501

Intrinsic noise in gene regulatory networks

M. Thattai and A. van Oudenaarden

PNAS 98, 8614

Download|20010501

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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

Awards

Current other activities


Group members

Alexander van Oudenaarden

Group Leader

Josi Peterson

Technician

Anna van Oudenaarden

Senior Researcher

Peter Zeller

Postdoc

Michael Vaninsberghe

Postdoc

Jeroen van den Berg

Postdoc

Amir Giladi

Postdoc

Cansu Koyunlar

Postdoc

Chih-Yao Chung

Postdoc

Euan Joly-Smith

Postdoc

Kseniia Sarieva

Postdoc

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

Mees van der Ent

PhD Student

Bert Jan Korte

PhD Student

Floris Leenders

Other

Widad Mammer Bouhou

Other

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Alumni – Postdoctoral Students

Alumni – Graduate Students