Sidinh Luc group - Properties of blood stem cells and their regulation

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.

About our research

To better understand the role of different types of blood stem cells (hematopoietic stem cells, HSCs) 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.

Group leader

Sidinh 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, 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.

Sidinh Luc about blood stem cells and hematologic diseases

Group members

 

Anne-Sofie Johansson

Sr 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 Somuncular

B.Sc., PhD 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.

Tsu-Yi (Franca) Su

PhD student

Open positions

Postdoctoral positions available. To apply, submit Cover letter and CV, including publication list and names of three references to sidinh.luc@ki.se

Former group members

  • Yiwei Ai, pre-PhD student
  • Hugo Brouwer, Master student
  • Sanchari Choudhury, Master student
  • Özge Dumral, Research Assistant
  • Prajakta Khalkar, Postdoc
  • Katarina Lyberg, Postdoc
  • Lisanne Schoutens, Master student
  • Christine Trautmann, B.Sc., Master student
  • Gizem Öztürk, Summer student

Research 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)
  • The Swedish Cancer Society (Cancerfonden)
  • European Hematology Association

Selected publications

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

Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors
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. . Nat Immunol. 2016 Oct 3. doi: 10.1038/ni.3576.

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

BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis.
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. Nature. 2015 Nov 12;527(7577):192-7. doi: 10.1038/ nature15521. Epub 2015 Sep 16.

Lymphomyeloid contribution of an immune-restricted progenitor emerging prior to definitive hematopoietic stem cells.
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. Cell Stem Cell. 2013 Nov 7;13(5):535-48.

Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire.
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. Cell Stem Cell. 2013 Oct 3;13(4):492-505.

The earliest thymic T cell progenitors sustain B cell and myeloid lineage potentials.
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. Nat Immunol. 2012 Feb 19;13(4):412-9

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

Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors.
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. Immunity. 2007 Apr;26(4):407-19.

*1 = shared first author.

2022-01-04
Sidinh Luc