Our laboratory takes a single cell systems biology approach to studying how haematopoietic stem cells ultimately generate all of the red and white blood cells of the immune system.
We are a very technology-driven lab with the philosophy that studying single cells at different functional and molecular levels, and integrating this information, will reveal the mechanisms behind their fate specification in health and disease. To this purpose, we perform single cell analysis in vivo using:
Combined, we anticipate this suite of tools will allow us to gain a high-resolution understanding into the principles and molecular mechanism governing development and the establishment of lineage fate in normal and cancerous tissues, with view to therapeutic interventions.
Australia, University of Queensland, BSc (Hons)
Australia, WEHI, PhD
2013, Young Tall Poppy of the Year, Australian Institute of Policy and Science
2013, International Travel Award, International Society of Experimental Hematology
2007, Participant, Lindau Nobel Laureates Meeting
2006, Premier’s Commendation for Medical Research, Victorian Government
2006, Seminar Prize, Walter and Eliza Hall Institute
2013, 2016 (x2), 2017 Project Grants, National Health and Medical Research Council
2015, Research Affiliate, Stem Cells Australia
2012, Research Grant, Human Frontiers Science Program
2010, Special Fellow, Leukemia & Lymphoma Society
2008, CJ Martin Fellow, National Health and Medical Research Council
Organising Committee, Human Cell Atlas
Strategic Development Group, Stem Cells Australia
Editorial Board, Cellular Immunology, Elsevier
Editorial Board, Frontiers in Molecular Innate Immunity
Member, Senior Technology Planning Group, Walter and Eliza Hall Institute
Schlitzer A, Sivakamasundari V, Chen J, Sumatoh HR, Schreuder J, Lum J, Malleret B, Zhang S, Larbi A, Zolezzi F, Renia L, Poidinger M, Naik S, Newell EW, Robson P, Ginhoux F. Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow. Nat Immunol. 2015 Jul;16(7):718-28 PMID: 26054720
Sathe P, Metcalf D, Vremec D, Naik SH, Langdon WY, Huntington ND, Wu L, Shortman K. Lymphoid tissue and plasmacytoid dendritic cells and macrophages do not share a common macrophage-dendritic cell-restricted progenitor. Immunity. 2014 Jul 17;41(1):104-15. PMID: 25035955.
Naik SH, Schumacher TN, Perie L. Cellular barcoding: a technical appraisal. Exp Hematol. 2014 Aug;42(8):598-608. PMID: 24996012.
Guilliams M, Ginhoux F, Jakubzick C, Naik SH, Onai N, Schraml BU, Segura E, Tussiwand R, Yona S. Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny. Nat Rev Immunol. 2014 Aug;14(8):571-8. PMID: 25033907.
Naik SH, Perie L, Swart E, Gerlach C, van Rooij N, de Boer RJ, Schumacher TN. Diverse and heritable lineage imprinting of early haematopoietic progenitors. Nature. 2013 Apr 11;496(7444):229-32. PMID: 23552896.
Gerlach C, Rohr JC, Perie L, van Rooij N, van Heijst JW, Velds A, Urbanus J, Naik SH, Jacobs H, Beltman JB, de Boer RJ, Schumacher TN. Heterogeneous differentiation patterns of individual CD8+ T cells. Science. 2013 May 3;340(6132):635-9. PMID: 23493421.
Naik SH. Demystifying the development of dendritic cell subtypes, a little. Immunol Cell Biol. 2008 Jul;86(5):439-52. PMID: 18414430.
Shortman K, Naik SH. Steady-state and inflammatory dendritic-cell development. Nat Rev Immunol. 2007 Jan;7(1):19-30. PMID: 17170756.
Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, Dakic A, Carotta S, O’Keeffe M, Bahlo M, Papenfuss A, Kwak JY, Wu L, Shortman K. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol. 2007 Nov;8(11):1217-26. PMID: 17922015.
Naik SH, Metcalf D, van Nieuwenhuijze A, Wicks I, Wu L, O’Keeffe M, Shortman K. Intrasplenic steady-state dendritic cell precursors that are distinct from monocytes. Nat Immunol. 2006 Jun;7(6):663-71. PMID: 16680143.
Cellular barcoding is a technology that allows the tracking of fate for hundreds of single stem cells simultaneously. Each progenitor is tagged with a unique DNA ‘stamp’ such that it is inherited by daughter cells and detected in progeny using DNA sequencing and computational analysis. In this way, we can compare barcode inheritance between cell types to infer their derivation from common vs. separate ancestors. We have used the technique to decipher the complexity of their individual fate and to reconstruct single cell lineage decisions in haematopoiesis (Naik, Nature, 2013).
We are now covering other aspects of haematopoiesis, including how these patterns change upon duress such as infection, and how modification of genetic regulators affects the output of single cells.
Team members: Dawn Lin, Jaring Schreuder
While cellular barcoding can determine the fate of many single cells in vivo, it cannot provide information on the shape of the ‘family tree’ where a single stem cell generates multiple cell types. In order to decipher this tree, one must track the entire process, including division and differentiation, and without loss of identity of individual cells.
To achieve this, we image microwells containing hematopoietic progenitors every 1-2 minutes for five days. In this system we can identify the acquisition of particular fates by cells by including fluorescently-labeled antibodies in the culture medium.
Team member: Dawn Lin
We have previously established that haematopoietic progenitors with very similar phenotypes often exhibit highly heterogeneous fates. Through clone-splitting experiments, where the fates of siblings from a single cell are assessed independently (for example, in two separate wells in vitro or transferred to two recipients in vivo), we have determined that this heterogeneous fate is often ‘imprinted’ (Naik et al. Nature. 2013).
We are tackling the nature of these molecular programs by performing high throughput single cell RNA sequencing – a relatively new but powerful technique – that can reveal single cell resolution differences that may account for differences in fate.
Team member: Jessica Tran