Where does blood come from?
The Forsberg lab focuses on stem cell fate decisions of the blood system. Hematopoietic stem cells are responsible for generating a life-long supply of mature blood cells. Each stem cell is capable of making all of the mature blood cell types with widely different functions: some blood cells specialize in carrying oxygen, others fight off infections, and still others prevent bleeding in the process of blood clotting. How does a stem cell decide which cell type to give rise to? Are these decisions made by the stem cell itself, by its descendant multipotent progenitors, or both? How are these decisions dysregulated to cause cancer and other disorders?
We tackle these questions from multiple angles - by in vivo and in vitro experimental approaches, by focusing on specific molecules as well as analyzing global changes. Ultimately, we want to understand the molecular determinants of hematopoietic stem cell fate decisions so that we can prevent and treat both genetic and acquired disorders of the hematopoietic system, including anemia, autoimmune disease, leukemias and lymphomas.
* = Forsberg lab member
*Beaudin AE, *Boyer SW, *Perez-Cunningham J, *Hernandez GE, Derderian SC, *Jujjavarapu C, *Aaserude E, MacKenzie T, and *Forsberg, EC. (2016). A transient developmental hematopoietic stem cell gives rise to innate-like B and T cells. Cell Stem Cell. Published online September 22, 2016
Preview in Cell Stem Cell: "From fetal to adult hematopoiesis with the "Flk" of a switch".
*Perez-Cunningham J, *Boyer SW, *Landon M and *Forsberg EC. (2016) Hematopoietic stem cell specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene. Experimental Hematology. Aug;44(8):755-764.e1. doi: 10.1016/j.exphem.2016.05.002. Epub 2016 May 13. PMID: 27185381
Larsen MC, N'Jai AU, Alexander DL, Rondelli CM, *Forsberg EC, Czuprynski CJ, Jefcoate CR.(2016) Cyp1b1‐mediated suppression of lymphoid progenitors in bone marrow by polycyclic aromatic hydrocarbons coordinately impacts spleen and thymus: a selective role for the Ah Receptor. Pharmacology Research & Perspectives 4 (4).
*Ugarte F, *Sousae S, Cinquin B, *Martin EM, *Krietsch J, *Sanchez G, *Inman M, *Tsang H, Warr M, Passegué E, Larabell C, and *Forsberg EC. (2015) Progressive chromatin condensation and H3K9 methylation regulate the differentiation of embryonic and hematopoietic stem cells. Stem Cell Reports. Nov 10;5(5):728-40.
Featured in “Hematopoiesis News” version 6.41, October 20, 2015
Zovein and *Forsberg, E.C. (2015) Hematopoietic development at high altitude: blood stem cells put to the test. Development. May 15;142(10):1728-32. Invited Commentary/Meeting Review
Hoeffel G, Chen J, Lavin Y, Low D, Almeida FF, See P, *Beaudin AE, Lum J, Low I, *Forsberg EC, Poidinger M, Zolezzi F, Larbi A, Ng LG, Chan JK, Greter M, Becher B, Samokhvalov IM, Merad M, Ginhoux F. (2015) C-myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity. Apr 21;42(4):665-78.
*Smith-Berdan S, *Nguyen A, *Hong MA, *Forsberg EC. (2015) ROBO4-Mediated Vascular Integrity Regulates the Directionality of Hematopoietic Stem Cell Trafficking. Stem Cell Reports. Feb 10;4(2):255-68.
Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM, Reynaud D, Alvarez S, Diolaiti ME, *Ugarte F, *Forsberg EC, Le Beau MM, Stohr BA, Méndez J, Morrison CG, Passegué E. (2014) Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells. Nature. Aug 14;512(7513):198-202.
Comment in: Nature 2014 Jul 30: Bartek, J. and Hodny, Z. “Old blood stem cells feel the stress”
Epelman S, Lavine KJ, *Beaudin AE, Sojka DK, Carrero JA, Calderon B, Brija T, Gautier EL, Ivanov S, Satpathy AT, Schilling JD, Schwendener R, Sergin I, Razani B, *Forsberg EC, Yokoyama WM, Unanue ER, Colonna M, Randolph GJ, Mann DL. (2014) Embryonic and Adult-Derived Resident Cardiac Macrophages Are Maintained through Distinct Mechanisms at Steady State and during Inflammation. Immunity. 2014 Jan 16;40(1):91-104.
*Beaudin, A.E., *Boyer, S.W., and *Forsberg, E.C. (2014) Flk2/Flt3 promotes both myeloid and lymphoid development by expanding non-self-renewing multipotent hematopoietic progenitor cells. Experimental Hematology. Mar;42(3):218-229.e4.
Highlighted in “In This Issue”, Experimental Hematology, March 2014
Hashimoto D, Chow A, Noizat C, Teo P, Beasley MB, Leboeuf M, Becker CD, See P, Price J, Lucas D, Greter M, Mortha A, *Boyer SW, *Forsberg EC, Tanaka M, van Rooijen N, García-Sastre A, Stanley ER, Ginhoux F, Frenette PS, Merad M. (2013) Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. Apr 18;38(4):792-804.
*Boyer, S.W., *Beaudin, A.E., and *Forsberg, E.C. (2012) Mapping differentiation pathways from hematopoietic stem cells using Flk2/Flt3 lineage tracing. Cell Cycle. Sep 1;11(17).
*Smith-Berdan, S., Schepers, K., *Ly, A., *Passegue, E., and *Forsberg, E.C. (2012) Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations. Cell Cycle. Feb 15;11(4).
*Boyer, S.W., *Schroeder, A.V., *Smith-Berdan, S., and *Forsberg, E.C. (2011) All hematopoietic cells are generated from hematopoietic stem cells through Flk2/Flt3-positive progenitor cells. Cell Stem Cell Jul 8;9(1):64-73.
Koeva, M., *Forsberg, E.C., and Stuart, J.M. (2011) Computational integration of homolog and pathway gene module expression reveals general stemness signatures. PLoS ONE 6(4): e18968.
*Smith-Berdan, S., *Nguyen, A., *Hassanein D, *Zimmer M, *Ugarte F, Ciriza J, Li D, García-Ojeda ME, Hinck L, and *Forsberg, E.C. (2011) Robo4 cooperates with Cxcr4 to specify hematopoietic stem cell localization to bone marrow niches. Cell Stem Cell 7;8(1):72-83.
Comment in: Cell Stem Cell 2011 Jan 7;8(1):6-7. Moore K. “A roundabout way to the niche”
Comment in: Nature 2011 Jan 20; 469(7330). Research Highlights, “Stem cells: Robo protein guide for cell transplants”
Selected for “Faculty of 1000”
Chang, E.1, Forsberg, E.C.1, Wu, J., Wang, B., Prohaska, S.S1., Allsopp, R., Weissman, I.L., and Cooke, J.P. (2010) Cholinergic activation of hematopoietic stem cells. Vasc Med. Oct;15(5):375- 85.
Marlow, R., Binnewies, M., Monica, S., Strickland, P., Forsberg, E.C., Li, D.Y., and Hinck, L. (2010) Vascular Robo4 restricts pro-angiogenic epithelial signaling in breast. Proc. Natl. Acad. Sci. U.S.A. 107(23):10520-5. Epub 2010 May 24.
Santaguida, M., Schepers, K., King, B., Sabnis, A.J., Forsberg, E.C., Attema, J.L., Braun, B.S., and Passegué, E. (2009). JunB protects against myeloid malignancies by limiting hematopoietic stem cell proliferation and differentiation without affecting self-renewal. Cancer Cell, 5: 341-52.