Joan Yuan Group
The dogma of hematopoiesis states that bone marrow hematopoietic stem cells (HSCs) produce a life time supply of blood and immune cells with limited lifespans and require continuous replenishment. However, antibody producing B cells in unperturbed adult mice are ontogenically distinct with a significant portion being generated within the first weeks of life and self-sustaining throughout adulthood. Our previous work has demonstrated a critical role for the Lin28b RNA binding protein in mediating a juvenile-to-adult switch in B cell output at the level of hematopoietic stem and progenitor cells (Yuan et al. Science, 2012, Kristiansen et al. Immunity, 2016). Our most recent paper identifies the central tolerance checkpoint as a major target of Lin28b regulation, demonstrating that Lin28b augments the positive selection of self-reactive B cells during a restricted developmental window in the first weeks of life (Vanhee et al. Science Immunology, 2019).
Currently, we are focused on pursuing the molecular, cellular and environmental determinants that control the timing and outcome of this developmental switch as well as its impact on host immunity and disease. By combining several lineage tracing approaches that track immune cells of distinct ontogeny across developmental time, with antigen receptor repertoire analyses, well-established immunization strategies, and cancer models, our work aims to address: how nature and nurture in the neonatal period shapes the formation of a complex and balanced immune system with important implications in life-long health and the origin of B cell cancers.
- Lin28b controls a neonatal to adult switch in B cell positive selection. Vanhee S, Åkerstrand H, Kristiansen TA, Datta S, Montano G, Vergani S, Lang S, Ungerbäck J, Doyle A, Olsson K, Beneventi G, Jensen CT, Bellodi C, Soneji S, Sigvardsson M, Jaensson Gyllenbäck E, Yuan J. Sci. Immunol. 2019 Sept; 4:39
- The influence of developmental timing on B cell diversity. Kristiansen TA, Vanhee S, Yuan J. Current Opinions in Immunology. 2018 Apr;51:7-13.
- PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice. Su D, Vanhee S, Soria R, Gyllenbäck EJ, Starnes LM, Højfeldt MK, Pedersen GK, Yuan J, Daniel JA. PNAS. 2017 Oct 31;114
- Cellular barcoding links B-1a B cell potential to a reversible fetal hematopoietic stem cell state at the single cell level. Kristiansen TA, Jaensson Gyllenbäck E, Zriwil A, Björklund T, Daniel JA, Sitnicka E, Soneji S, Bryder D, Yuan J. Immunity. 2016 Aug. 45;346-357
- Lin28b reprograms adult bone marrow hematopoietic progenitors to mediate fetal-like lymphopoiesis. Yuan J, Nguyen CK, Liu X, Kanellopoulou C, Muljo SA. Science. 2012 Mar 9;335(6073):1195-200.
Phone: +46 (0)46 222 04 30
Mobile: +46 (0)72 586 88 02
E-mail: joan [dot] yuan [at] med [dot] lu [dot] se
Sneh Lata Gupta
sneh_lata [dot] gupta [at] med [dot] lu [dot] se
stefano [dot] vergani [at] med [dot] lu [dot] se
trine [dot] kristiansen [at] med [dot] lu [dot] se
hugo [dot] akerstrand [at] med [dot] lu [dot] se
karin [dot] olsson [at] med [dot] lu [dot] se
alexander [dot] doyle [at] med [dot] lu [dot] se
giorgia [dot] montano [at] med [dot] lu [dot] se
niklas [dot] krausse [dot] 0471 [at] med [dot] lu [dot] se
Division of Molecular Hematology
Lund Stem Cell Center, Lund University
SE-221 84 Lund
Room: BMC, B1215b