Sidinh Luc group

 

The blood system is maintained and replenished by rare blood stem cells throughout life. Until recently, the blood stem cell population was considered to be functionally uniform, but new findings suggest the presence of different stem cell subsets that are biased in their contribution to individual blood lineages. 

The functional importance of having different types of blood stem cells is not well understood and the mechanisms that regulate them have not been well characterized. Our research program primarily focuses on hematopoietic stem cells in normal development. Detailed knowledge of blood formation and the different stem cell types will increase our fundamental understanding of how hematologic diseases may develop and how they may be treated.

Members

Sidinh LucSidinh Luc, Ph.D., Group leader, Assistant Professor
Sidinh Luc was recruited to Karolinska Institutet in 2017. Her graduate studies were done at Lund University, Sweden and University of Oxford, UK, and she received a Ph.D. degree in Stem Cell Biology from Lund University, Sweden in 2011. After graduate school she continued her research studies as a postdoctoral fellow at Boston Children’s Hospital/Dana-Farber Cancer Institute/Harvard Medical School in Boston (2011-2016), before returning to Sweden to start her own research group.

Ann-Sofie Johansson, Lab manager
Anne-Sofie received her PhD in 2007 from Karolinska Institutet (KI) for her work on effects of ethanol on inflammation and cell functions. After her PhD she did a postdoc at the department of Neuroscience (KI), where she gained experience about the circadian rhythms and the circadian molecular clock and how they may be altered in disease. She joined HERM in 2014, and Luc group in 2017. 

 

Ece SomuncularEce Somuncular, B.Sc., Research assistant, Pre-Ph.D. student
Ece Somuncular got her Bachelor of Science degree in Molecular Biology and Genetics from the Izmir Institute of Technology in Turkey in 2016. She joined the Luc group in 2017 as a Research assistant and Pre-Ph.D. graduate student.


 

Yiwei Ai Yiwei Ai, Pre-Ph.D student
Yiwei Ai received his M.D. and M.Sc from Harbin Medical University, China in 2016. He joined the Luc group in 2017. His research focuses on epigenetic regulation in hematopoietic stem cells in a lineage perspective.



Research program

The functional significance of having different types of hematopoietic stem cells (HSCs) is not well understood. The regulatory mechanisms that are involved in determining the identity of different types of blood stem cells are also not well characterized.

To better understand the role of different HSC subsets in the hematopoietic system, we are studying the molecular, behavioral and functional differences of distinct types of HSCs throughout development. These studies employ a combination of genetic labelling tools, advanced flow cytometry and sequencing techniques.

To understand the molecular mechanisms that regulate different types of HSCs we have focused on exploring the epigenetic processes that are important in HSC bias and lineage commitment. Using advanced molecular biology tools and genome editing techniques, as well as genetically modified mouse models we are aiming to identify the critical epigenetic factors determining the functional properties of the HSC subsets.

The long-term goal of our studies is to discover novel factors and associated pathways that are important in development of hematologic diseases and ultimately be of therapeutic and prognostic value.

Financial support

  • The Knut och Alice Wallenberg Foundation (Knut och Alice Wallenbergs stiftelse)
  • The Swedish Research Council (Vetenskapsrådet)
  • Dr Åke Olsson foundation
  • Åke Wiberg foundation
  • The Swedish Childhood Cancer Foundation (Barncancerfonden)
  • Strategic Research Area Stem Cells and Regenerative Medicine (Junior Grant)

Selected publications

Smith EC, Luc S, Croney DM, Woodworth MB, Greig LC, Fujiwara Y, Nguyen M, Sher F, Macklis JD, Bauer DE, Orkin SH. Strict in vivo specificity of the Bcl11a erythroid enhancer. Blood 2016 :blood-2016-08-736249; doi:10.1182/blood-2016-08-736249

Luis TC1, Luc S1, Mizukami T, Boukarabila H, Thongjuea S, Woll PS, Azzoni E, Giustacchini A, Lutteropp M, Bouriez-Jones T, Vaidya H, Mead AJ, Atkinson Deborah, Böiers C, Carrelha J, Macaulay IC, Patient R, Geissmann F, Nerlov C, Sandberg R, de Bruijn MFTR, Blackburn CC, Godin I, Jacobsen SEW. Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors. Nat Immunol. 2016 Oct 3. doi: 10.1038/ni.3576.

Luc S, Huang J, McEldoon JL, Somuncular E, Li D, Rhodes, C, Mamoor S, Hou S, Xu J, Orkin SH. Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. Cell Reports. 2016 Sep 20;16(12):3181-94. doi: 10.1016/j.celrep.2016.08.064

Canver MC, Smith EC, Sher F, Pinello L, Sanjana NE, Shalem O, Chen DD, Schupp PG, Vinjamur DS, Garcia SP, Luc S, Kurita R, Nakamura Y, Fujiwara Y, Maeda T, Yuan GC, Zhang F, Orkin SH, Bauer DE. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015 Nov 12;527(7577):192-7. doi: 10.1038/ nature15521. Epub 2015 Sep 16.

Böiers C, Carrelha J, Lutteropp M, Luc S, Green JC, Azzoni E, Woll PS, Mead AJ, Hultquist A, Swiers G, Perdiguero EG, Macaulay IC, Melchiori L, Luis TC, Kharazi S, Bouriez-Jones T, Deng Q, Ponten A, Atkinson D, Jensen CT, Sitnicka E, Geissmann F, Godin I, Sandberg R, de Bruijn MF, Jacobsen SE. Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells. Cell Stem Cell. 2013 Nov 7;13(5):535-48.

Guo G, Luc S, Marco E, Lin TW, Peng C, Kerenyi MA, Beyaz S, Kim W, Xu J, Das PP, Neff T, Zou K, Yuan GC, Orkin SH. Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire. Cell Stem Cell. 2013 Oct 3;13(4):492-505.

Luc S, Luis TC, Boukarabila H, Macaulay IC, Buza-Vidas N, Bouriez-Jones T, Lutteropp M, Woll PS, Loughran SJ, Mead AJ, Hultquist A, Brown J, Mizukami T, Matsuoka S, Ferry H, Anderson K, Duarte S, Atkinson D, Soneji S, Domanski A, Farley A, Sanjuan-Pla A, Carella C, Patient R, de Bruijn M, Enver T, Nerlov C, Blackburn C, Godin I, Jacobsen SEW. The earliest thymic T cell progenitors sustain B cell and myeloid lineage potentials. Nat Immunol. 2012 Feb 19;13(4):412-9

Luc S1, Anderson K1, Kharazi S1, Buza-Vidas N1, Böiers C, Jensen CT, Ma Z, Wittman L, Jacobsen SEW. Downregulation of Mpl marks the transition to lymphoid-primed multipotent progenitors with gradual loss of granulocyte-monocyte potential. Blood. 2008 Apr 1;111(7):3424-34.

Månsson R1, Hultquist A1, Luc S1, Yang L1, Anderson K, Kharazi S, Al-Hashmi S, Liuba K, Thorén L, Adolfsson J, Buza-Vidas N, Qian H, Soneji S, Enver T, Sigvardsson M, Jacobsen SE. Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors. Immunity. 2007 Apr;26(4):407-19.

*1 = shared first author. 
HematologyStem cells