Natarajan Laboratory
Investigating cell fate paradigms and transcriptional regulation during mammalian development and differentiation
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Our research

The Natarajan laboratory We are interested in the fundamental process of cell fate specification during mammalian development and differentiation at single-cell level. The group aims to understand general paradigms of cell state and fate specification, with a particular interest in transcriptional and epigenetic regulatory networks, and their crosstalk with cell cycle, metabolism and fundamental cellular processes.

We have a interdisciplinary foundation and combine wet-lab experiments with theoretical models and computational approaches at single-cell and bulk level to uncover principles governing cell fate decisions, and their consequences in development and disease. We leverage different developmental (ESCs/hiPSCs), differentiation (CNS, immune) models alongside molecular, cellular and computational approaches.



Areas of research

Cell cycle control of transcriptional regulation

We study how transcriptional regulation is governed globally during cell cycle and across phases in ESCs/iPSCs at single-cell level.
We utilise cell cycle sensors combined with candidate gene perturbation and single-cell profiling to understand different mechanisms involved in cell cycle regulation of pluripotency and differentiation.

Cell fate specification and dynamics during differentiation

Distinct cell cycle changes accompany stem cell differentiation and can drive cell-fate responses.
We combine state-of-art single-cell genomics and computational tools to investigate transcriptional and epigenetic changes that accompany cell-fate specification.

New methods for single-cell biology

We have a strong interest in development, extension and utilisation of new experimental and computational methods for single-cell biology.
Working closely with collaborators, we develop new computational tools that integrate measurements from several single-cell technologies.

Our Team

Kedar Natarajan

Group Leader

Malvika Sudhakar

Postdoctoral Fellow

Gergo Kovacs

Postdoctoral Fellow

Rahul Agrawal

Postdoctoral Fellow

Lorenzo Guerci

PhD Candidate

Yee Ying Lim

Research Assistant

Lea Jerman-Plesec

Research Assistant

William Echwald

Masters thesis

Alumni

Masters : Tomasso Asquini, Konrad Uscilo, Da Eun Lee, Valentina Hekimova, Maja Brask, Sophia Hald

Bachelors : Maja Brask, Felix Pedersen

PhD : HyunTae Choi, Simon Jakobsen, Andreas Moller

Postdoc: Deyong Zhu

Join us!



We welcome enquiries from highly interdisciplinary, motivated and ambitious candidates.

Postdocs candidates with strong background and interest in areas of single-cell genomics, computational biology and machine learning are welcome to enquire informally on lab projects. We encourage and support applications to Danish and international funding agencies. Please email a tailored cover letter, CV, publication record and details of two references

Interested PhD students are also welcome to enquire about applying for funding. Please email directly.

Publications

2023

CRISPR-Cas12a-integrated transgenes in genomic safe-harbors retain high expression in human hematopoietic iPSC-derived lineages and primary cells

Vlassis A, Jensen TL, Mohr M, Jedrzejczyk DJ, Meng X, Kovacs G, Gómez MM, Barghetti A, Sergi M Abad SM, Baumgartner RF, Natarajan KN, Nielsen LK, Warnecke T, Gill RT
Published in: iScience

Exploration of cell state heterogeneity using single-cell proteomics through sensitivity-tailored data-independent acquisition

Lee J, Møller AF, Chae S, Bussek A, Park TJ, Kim Y, Lee HS, Pers TH, Kwon T, Sedzinski J, Natarajan KN
Published in: Nature Communications

A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development

Lee J, Møller AF, Chae S, Bussek A, Park TJ, Kim Y, Lee HS, Pers TH, Kwon T, Sedzinski J, Natarajan KN
Published in: Science Advances

Oncogenic signaling pathways in pancreatic ductal adenocarcinoma.

Agrawal R and Natarajan KN
Published in: Advances in Cancer Research

Matching queried single-cell open-chromatin profiles to large pools of single-cell transcriptomes and epigenomes for reference supported analysis.

Mishra S, Pandey N, Chawla S, Sharma M, Chandra O, Jha IP, SenGupta D, Natarajan KN# Kumar V#
Published in: Genome Research

Matching queried single-cell open-chromatin profiles to large pools of single-cell transcriptomes and epigenomes for reference supported analysis.

G Weng, J Kim, KN Natarajan#, KJ Won#
Published in: bioRxiv

2022

Cell Competition in Carcinogenesis.

Madan E, Palma AM, Vudatha V, Trevino JG, Natarajan KN, Winn RA, Won KJ, Graham TA, Drapkin R, McDonald SAC, Fisher PB, Gogna R
Published in: Cancer Research

PPARγ lipodystrophy mutants reveal intermolecular interactions required for enhancer activation.

Madsen MS, Broekema MF, Madsen MR, Koppen A, Borgman A, Gräwe C, Thomsen EGK, Westland D, Kranendonk MEG, Koerkamp MG, Hamers N, Bonvin AMJJ, Pittol JMR, Natarajan KN, Kersten S, Holstege FCP, Monajemi H, van Mil SWC, Vermeulen M, Kragelund BB, Cassiman D, Mandrup S, Kalkhoven E
Published in: Nature Communication

TENET: gene network reconstruction using transfer entropy reveals key regulatory factors from single cell transcriptomic data.

Kim J, Jakobsen ST, Natarajan KN# and Won KJ#
Published in: Nucleic Acid Research.

2021

TENET: gene network reconstruction using transfer entropy reveals key regulatory factors from single cell transcriptomic data.

Kim J, Jakobsen ST, Natarajan KN# and Won KJ#
Published in: Nucleic Acid Research.

2020

Predicting gene regulatory networks from cell atlases

Moeller AF and Natarajan KN#
Published in: Life Science Alliance.

SBML Level 3: an extensible format for the exchange and reuse of biological models

Keating SM, Waltemath D, et al., and SBML Level 3 Community members
Published in: Molecular Systems Biology.

Transcriptional dynamics of hepatic sinusoid‐associated cells after liver injury.

Terkelsen MK, Bendixen SM, Hansen D, Scott EAH, Moeller AF, Nielsen R, Mandrup S, Schlosser A, Andersen TL, Sorensen GL, Krag A, Natarajan KN, Detlefsen S, Dimke H, Ravnskjaer K
Published in: Hepatology.

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

Cuomo SE, Seaton DD, McCarthy DJ, Martinez I, Bonder MJ, Garcia-Bernardo J, Amatya S, Madrigal P, Isaacson A, Buettner F, Knights A, Natarajan KN, HipSci Consortium, Vallier L, Marioni JC, Chhatriwala M, Stegle O.
Published in: Nature Communications.

Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development.

Oatley M, Bolukbasi OV, Svensson V, Shvartsman M, Ganter K, Zirngibl K, Pavlovich PV, Milchevskaya V, Foteva V, Natarajan KN, Baying B, Benes V, Patil KR, Teichmann SA, Lancrin C
Published in: Nature Communications.

2019

The Malaria Cell Atlas: Single parasite transcriptomes across the complete Plasmodium life cycle.

Howick VM, Russell AJC, Andrews T, Heaton H, Reid AJ, Natarajan K, Butungi H, Metcalf T, Verzier LH, Rayner JC, Berriman M, Herren JK, Billker O, Hemberg M, Talman AM, Lawniczak MKN.
Published in: Science.

Comparative analysis of sequencing technologies for single-cell transcriptomics.

Natarajan KN*#, Miao Z*, Jiang M*, Huang X, Zhou H, Xie J, Wang C, Qin S, Zhao Z, Wu L, Yang N, Li B, Hou Y, Liu S, Teichmann SA#.
Published in: Genome Biology.

Single-Cell Tagged Reverse Transcription (STRT-Seq).

Natarajan KN#.
Published in: Methods in Molecular Biology.

2018

A rapid and robust method for single cell chromatin accessibility profiling.

Chen X, Miragaia RJ, Natarajan KN, Teichmann SA.
Published in: Nature Communications.

Genome-wide analyses reveal the IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation.

Pramanik J, Chen X, Kar G, Henriksson J, Gomes T, Park JE, Natarajan K, Meyer KB, Miao Z, McKenzie ANJ, Mahata B, Teichmann SA.
Published in: Genome Medicine.

Distinctive features of lincRNA gene expression suggest widespread RNA-independent functions.

Tuck AC, Natarajan KN, Rice GM, Borawski J, Mohn F, Rankova A, Flemr M, Wenger A, Nutiu R, Teichmann SA, Bühler M
Published in: Life Science Alliance.

2017

Single cell transcriptomics of pluripotent stem cells: reprogramming and differentiation.

Natarajan KN*#, Teichmann SA, Kolodziejczyk AA.
Published in: Current Opinion of Genetics and Development.

Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression.

Kar G, Kim JK, Kolodziejczyk AA, Natarajan KN, Torlai Triglia E, Mifsud B, Elderkin S, Marioni JC, Pombo A, Teichmann SA
Published in: Nature Communications.

SC3: consensus clustering of single-cell RNA-seq data

Kiselev VY, Kirschner K, Schaub MT, Andrews T, Yiu A, Chandra T, Natarajan KN, Reik W, Barahona M, Green AR, Hemberg M.
Published in: Nature Methods.

Cell biology: tracking a cell’s cycle

Natarajan KN*# and Teichmann SA (Journalistic feature)
Published in: Nature methods.

Postdocs: What would you tell your younger self.

Natarajan KN*# (Special feature comment)
Published in: Cell.

Power analysis of single-cell RNA-sequencing experiments.

Svensson V*, Natarajan KN*, Ly LH, Miragaia RJ, Labalette C, Macaulay IC, Cvejic A, Teichmann SA.
Published in: Nature Methods.

2016

Single-cell analysis of CD4+ T-cell differentiation reveals three major cell states and progressive acceleration of proliferation.

Proserpio V, Piccolo A, Haim-Vilmovsky L, Kar G, Lönnberg T, Svensson V, Pramanik J, Natarajan KN, Zhai W, Zhang X, Donati G, Kayikci M, Kotar J, McKenzie AN, Montandon R, Billker O, Woodhouse S, Cicuta P, Nicodemi M, Teichmann SA.
Published in: Genome Biology.

The systems biology format converter.

Rodriguez N, Pettit JB, Dalle Pezze P, Li L, Henry A, van Iersel MP, Jalowicki G, Kutmon M, Natarajan KN, Tolnay D, Stefan MI, Evelo CT, Le Novère N.
Published in: BMC Biology.

2015

Single Cell RNA-Sequencing of Pluripotent States Unlocks Modular Transcriptional Variation.

Kolodziejczyk AA, Kim JK, Tsang JC, Ilicic T, Henriksson J, Natarajan KN, Tuck AC, Gao X, Bühler M, Liu P, Marioni JC, Teichmann SA
Published in: Cell Stem Cell.

Computational assignment of cell-cycle stage from single-cell transcriptome data.

Scialdone A, Natarajan KN, Saraiva LR, Proserpio V, Teichmann SA, Stegle O, Marioni JC, Buettner F
Published in: Methods.

Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells.

Buettner F*, Natarajan KN*, Casale FP, Proserpio V, Scialdone A, Theis FJ, Teichmann SA, Marioni JC, Stegle O.
Published in: Nature Biotechnology.

2014

BioModels: ten-year anniversary.

Chelliah V, Juty N, Ajmera I, Ali R, Dumousseau M, Glont M, Hucka M, Jalowicki G, Keating S, Knight-Schrijver V, Lloret-Villas A, Natarajan KN, Pettit JB, Rodriguez N, Schubert M, Wimalaratne SM, Zhao Y, Hermjakob H, Le Novère N, Laibe C
Published in: Nucleic Acid Research.

2011

The System Biology Format Converter.

Jalowicki G, Rodriguez N, Kutmon M, Pettit JB, Li L, Henry A, Natarajan KN, Laibe C, Evelo CT, Novere NL
Published in: Nature Precedings.

Funding

Our research is possible due to generous support form:



Contact Us

We are part of DTU Bioengineering at Technical University of Denmark.

Transcriptional regulation and Single-cell systems genomics,
DTU Bioengineering
Technical University of Denmark
Søltofts Plads, DK-2800 Kgs. Lyngby

kenana@dtu.dk