Prof Shalin Naik, Lab Head | WEHI Researcher Profile

Q: Using cellular barcoding to track individual stem and progenitor cells in vivo

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.

Q: Constructing pedigrees from single stem cells using long-term imaging

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.

Q: Using single cell RNA-sequencing to identify lineage programs

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.

About

I wear many hats, having been trained in immunology and haematopoiesis, but with a passion for developing new tools to tackle fundamental unanswered questions in biology.

Education

Grants and funding

Publications

Selected publications from Prof Shalin Naik

Tran VL, Haltalli MLR, Li J, Lin DS, Yamashita M, Naik SH, Rothenberg EV. Ever-evolving insights into the cellular and molecular drivers of lymphoid cell development. Experimental Hematology. 2024;140:10.1016/j.exphem.2024.104667

Stonehouse OJ, Biben C, Weber TS, Garnham A, Fennell KA, Farley A, Terreaux AF, Alexander WS, Dawson MA, Naik SH, Taoudi S. Clonal analysis of fetal hematopoietic stem/progenitor cells reveals how post-transplantation capabilities are distributed. Stem Cell Reports. 2024;19(8):10.1016/j.stemcr.2024.07.003

Audiger C, Laâbi Y, Nie J, Gibson L, Wilson-Annan J, Brook-Carter P, Kueh A, Harris AW, Naik S, Nutt SL, Strasser A, Adams JM, Bouillet P, Chopin M. Mis-expression of GATA6 re-programs cell fate during early hematopoiesis. Cell Reports. 2024;43(5):10.1016/j.celrep.2024.114159

Brown DV, Anttila CJA, Ling L, Grave P, Baldwin TM, Munnings R, Farchione AJ, Bryant VL, Dunstone A, Biben C, Taoudi S, Weber TS, Naik SH, Hadla A, Barker HE, Vandenberg CJ, Dall G, Scott CL, Moore Z, Whittle JR, Freytag S, Best SA, Papenfuss AT, Olechnowicz SWZ, MacRaild SE, Wilcox S, Hickey PF, Amann-Zalcenstein D, Bowden R. A risk-reward examination of sample multiplexing reagents for single cell RNA-Seq. Genomics. 2024;116(2):10.1016/j.ygeno.2024.110793

Cao H, Naik SH, Amann-Zalcenstein D, Hickey P, Salim A, Cao B, Nilsson SK, Keightley MC, Lieschke GJ. Late fetal hematopoietic failure results from ZBTB11 deficiency despite abundant HSC specification. Blood Advances. 2023;7(21):10.1182/bloodadvances.2022009580

Lutz MB, Ali S, Audiger C, Autenrieth SE, Berod L, Bigley V, Cyran L, Dalod M, Dörrie J, Dudziak D, Flórez-Grau G, Giusiano L, Godoy GJ, Heuer M, Krug AB, Lehmann CHK, Mayer CT, Naik SH, Scheu S, Schreibelt G, Segura E, Seré K, Sparwasser T, Tel J, Xu H, Zenke M. Guidelines for mouse and human DC generation. European Journal of Immunology. 2023;53(11):10.1002/eji.202249816

Borger JG, Ng AP, Anderton H, Ashdown GW, Auld M, Blewitt ME, Brown DV, Call MJ, Collins P, Freytag S, Harrison LC, Hesping E, Hoysted J, Johnston A, McInneny A, Tang P, Whitehead L, Jex A, Naik SH. Artificial intelligence takes center stage: exploring the capabilities and implications of ChatGPT and other AI‐assisted technologies in scientific research and education. Immunology and Cell Biology. 2023;101(10):10.1111/imcb.12689

Serrano A, Weber T, Berthelet J, El-Saafin F, Gadipally S, Charafe-Jauffret E, Ginestier C, Mariadason JM, Oakes SR, Britt K, Naik SH, Merino D. Experimental and spontaneous metastasis assays can result in divergence in clonal architecture. Communications Biology. 2023;6(1):10.1038/s42003-023-05167-5

Audiger C, Tomei S, Naik SH. tDCs — a distinct subset with dual functional and developmental roles. Nature Immunology. 2023;24(8):10.1038/s41590-023-01565-3

Perriman L, Tavakolinia N, Jalali S, Li S, Hickey PF, Amann-Zalcenstein D, Ho WWH, Baldwin TM, Piers AT, Konstantinov IE, Anderson J, Stanley EG, Licciardi PV, Kannourakis G, Naik SH, Koay H-F, Mackay LK, Berzins SP, Pellicci DG. A three-stage developmental pathway for human Vγ9Vδ2 T cells within the postnatal thymus. Science Immunology. 2023;8(85):10.1126/sciimmunol.abo4365