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.

Postdoctoral positions in stem cell research available

We're accepting postdoctoral applications for our new IRACDA postdoctoral training  program! Please email Dr. Forsberg if you are interested in performing your IRACDA research in the Forsberg lab. Check out details here: https://ibsc.ucsc.edu/iracda-training-program/

NOW OPEN: Research Specialist position for a candidate with strengths in cell and molecular biology, including plasmid cloning and library generation. Please apply here: https://recruit.ucsc.edu/JPF00930

News                                                                                         

In press: Check out our new stories on aging and megakaryocytes, chromatin accessibility, and effects of acute loss of Robo4 on HSC trafficking. Congrats to our researchers for excellent advances in hematopoiesis.

Congratulations to Dr. Bryce Manso and Dr. Alessandra Rodriguez y Baena for your selection as an IRACDA postdoctoral fellows! 

New publication in Cell on An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis, Poscalbo, et. al. Cell, 2024.

Events

"They grow up so fast: Development and aging of blood" - watch video here!

Links

• GIVING 2024: learn about how to donate here: https://www.santacruzworks.org/news/ucsc-giving-day
• Postdoctoral fellow positions: http://www2.ucsc.edu/ahr/academic_employment/bulletin_flyers_originaldocs_pdfs/07-08/T08-30.pdf
• UCSC Institute for the Biology of Stem Cells (IBSC): https://stemcell.soe.ucsc.edu/

Publications

* = Forsberg lab member (past or present)

• *Poscablo DM, *Worthington AK, *Smith-Berdan S, *Rommel MGE, *Manso BA, *Adili R, Mok L, Reggiardo RE, *Cool T, *Mogharrab R, *Myers J, *Dahmen S, *Medina P, *Beaudin AE, *Boyer SW, Holinstat M, Jonsson VD, *Forsberg EC. (2024) An age-progressive platelet differentiation path from hematopoietic stem cells causes exacerbated thrombosis. Cell. Jun 6;187(12):3090-3107.e21. PMID: 38749423
• *Manso BA, *Rodriguez Y Baena A, *Forsberg EC. From Hematopoietic Stem Cells to Platelets: Unifying Differentiation Pathways Identified by Lineage Tracing Mouse Models.
  Cells. (2024) Apr 19;13(8):704. PMID: 38667319
• *Martin EW, *Rodriguez Y Baena A, Reggiardo RE, *Worthington AK, *Mattingly CS, *Poscablo DM, *Krietsch J, McManus MT, Carpenter S, Kim DH, *Forsberg EC. Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny. Stem Cells. (2023) May 15;41(5):520-539. PMID: 36945732
• *Worthington AK, *Forsberg EC. A CRISPR view of hematopoietic stem cells: Moving innovative bioengineering into the clinic.  Am J Hematol. (2022) Sep;97(9):1226-1235.  PMID: 35560111
• *Rodriguez y Baena A, *Rajendiran S, *Manso BA.,  *Krietsch J, *Boyer, SW.,  *Kirschmann J, and *Forsberg, EC. (2022) New transgenic mouse models enabling pan-hematopoietic or selective hematopoietic stem cell depletion in vivo. Sci.Rep. 12: 3156. PMID: 35210475

• *Cool T, *Rodriguez Y Baena A, *Forsberg EC. (2022) Clearing the Haze: How Does Nicotine Affect Hematopoiesis before and after Birth? 14(1):184. PMID: 35008347

• *Worthington AK, *Cool T, *Poscablo DM, *Hussaini A, *Beaudin AE, *Forsberg EC. (2022) 

  IL7Rα, but not Flk2, is required for hematopoietic stem cell reconstitution of tissue-resident lymphoid cells. Development. 149(8):dev200139. PMID: 35072209

• *Worthington AK and  ^*Forsberg EC. (2022) A CRISPR view of hematopoietic stem cells: Moving innovative bioengineering into the clinic. Am J Hematol. 97(9): 1226–1235. PMID: 35560111

• *Poscablo DM and *Forsberg EC. (2021) The Clot Thickens: Recent Clues on Hematopoietic Stem Cell Contribution to Age-Related Platelet Biology Open New Questions. Adv Geriatr Med Res. 3(4):e210019.
  

• *Rodriguez Y Baena A, *Manso BA, *Forseberg, EC. (2021) CFU-S assay: a historical single-cell assay that offers modern insight into clonal hematopoiesis. Exp Hematology. 104:1-8. PMID: 34688837

• *Martin EW, *Krietsch J, Reggiardo RE, *Sousae R, Kim DH, *Forsberg EC. (2021) Chromatin accessibility maps provide evidence of multilineage gene priming in hematopoietic stem cells. Epigenetics Chromatin. 14(1):2. PMID: 33407811

• *Smith-Berdan S, *Bercasio A, *Kramer L, *Petkus B, Hinck L, *Forsberg EC. (2021) Acute and endothelial-specific Robo4 deletion affect hematopoietic stem cell trafficking independent of VCAM1. PLos1. 16(8):e0255606. PMID: 34388149

• *Poscablo DM, *Worthington AK, *Smith-Berdan S, *Forsberg EC. (2021) Megakaryocyte progenitor cell function is enhanced upon aging despite the functional decline of aged hematopoietic stem cells. Stem Cell Reports. 16(6):1598-1613. PMID: 34019813

• *Cool T, *Worthington A, *Poscablo D, *Hussaini A, *Forsberg EC. (2020) Interleukin 7 receptor is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells. Exp Hematology. 90:39-45.e3. PMID: 32916215

• *Cool T, *Forsberg, EC. (2019) Chasing Mavericks: The quest for defining developmental waves of hematopoiesis. Curr Top Dev Bio. 132:1-29. PMID: 30797507

• *Smith-Berdan S, *Bercasio A, *Rajendiran S, *Forsberg EC. (2019) Viagra Enables Efficient, Single-Day Hematopoietic Stem Cell Mobilization. Stem Cell Reports. 13(5):787-792. PMID: 31607567

• Farhy C, Hariharan S, Ylanko J, van Woudenberg L, Cimadamore F, *Ugarte F, *Forsberg EC, Huang C-T, Andrews D, Terskikh A. (2019) Improving drug discovery using image-based multiparametric analysis of the epigenetic landscape. Elife. Oct 22;8. pii: e49683. PMID: 31637999

• Leung G, *Cool T, Valencia C, *Worthington A, Beaudin A and *Forsberg EC. (2019) The lymphoid-associated interleukin 7 receptor (IL-7R) regulates tissue resident macrophage development. Development. 146(14). pii: dev176180. PMID: 31332039

• *Boyer S, *Rajendiran S, *Beaudin A, *Smith-Berdan S, Muthuswamy P, *Perez-Cunningham J, *Martin EW, *Cheung C, *Tsang H, *Landon M and *Forsberg EC. (2019) Clonal and quantitative in vivo assessment of hematopoietic stem and progenitor cell differentiation reveals strong erythoid potential of multipotent cells. Stem Cell Reports. 12(4):801-815. PMID: 30905737
  

  GITHUB resource: https://github.com/cforsberg/Boyer-Stem-Cell-Reports-2019

• *Cool T and *Forsberg EC. (2019) Chasing Mavericks: The quest for defining developmental waves of hematopoiesis. Current Topics in Developmental Biology. Invited Review. 132:1-29. PMID: 30797507
  

• Cole C, Byrne A, *Beaudin AE, *Forsberg EC, and Vollmers C. (2018) Tn5Prime, a Tn5 based 5' capture method for single cell RNA-seq. Nucleic Acids Res. 2018 Jun 1;46(10):e62. PMID: 29548006 PMCID: PMC6007450

• Byrne A, *Beaudin AE, Olsen HE, Jain M, Cole C, Palmer T, DuBois RM, *Forsberg EC, Akeson M, and Vollmers C (2017) Nanopore Long-Read RNAseq Reveals Widespread Transcriptional Variation Among Single B cells. Nature Communications.  Jul 19;8:16027. PMID: 28722025 PMCID: PMC5524981

• *Beaudin, AE and *Forsberg, EC. (2016) To B1a or not to B1a: do hematopoietic stem cells contribute to tissue-resident immune cells? Blood. 128(24):2765-2769. Review. PMID: 27799163 PMCID: PMC5159701

• *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. 19(6):768-783. PMID: 27666010 PMCID: PMC5524382 

              Preview in: Cell Stem Cell. 2016;19(6):673-674. Stijn Vanhee and Joan Yuan “Fetal to

              Adult Hematopoiesis with the ‘Flk’ of a Switch”

              Special highlight review in: Stem Cell Investig. 2017;4(25). Bridget Waas and Ivan Maillard

              “Fetal hematopoietic stem cells are making waves”

              Selected for “Faculty of 1000” by two independent F1000 members

• *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.

                    Comment in: Immunity 2015 April 21: Schneider, C. and Kopf, M. “tEMPting Fate MaYBe the Solution”

• *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.

                    Cover image

• 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

• *Ugarte, F. and *Forsberg, E.C. (2013) Haematopoietic stem cell niches: new insights inspire new questions. EMBO J. Oct 2;32(19):2535-2547. Invited review.

• 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.

Selected for “Faculty of 1000” 

• 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.

Cover image
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.

• *Forsberg, E.C. and *Smith-Berdan, S. (2009) Parsing the niche code: the molecular mechanisms governing hematopoietic stem cell adhesion and differentiation. Haematologica 94(11):1477-81.  

Cover image

• Forsberg, E.C., Passegue, E1., Prohaska, S.S1., Wagers, A.J1., Koeva, M., Stuart, J.M., and Weissman, I.L. (2009) Molecular signatures of quiescent and mobilized hematopoietic stem cells and leukemic stem cells. PLoS One Jan 20;5(1):e8785.
• Ooi, A.G.L., Karsunky, H., Majeti, R., Butz, S., Vestweber, D., Ishida, T., Quertermous, T., Weissman, I.L., and Forsberg, E.C. (2008) The adhesion molecule ESAM1 is a selective marker for hematopoietic stem cells. Stem Cells. 2008 Dec 11, Epub ahead of print.
• Attema JL, Papathanasiou P, Forsberg EC, Xu J, Smale ST, Weissman IL. Epigenetic characterization of hematopoietic stem cell differentiation using miniChIP and bisulfite sequencing analysis. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12371-6. Epub 2007 Jul 18.
• Forsberg EC, Bhattacharya D, Weissman IL. Hematopoietic stem cells: expression profiling and beyond. Stem Cell Rev. 2006;2(1):23-30. Review.
• Forsberg EC, Serwold T, Kogan S, Weissman IL, Passegué E. New evidence supporting megakaryocyte-erythrocyte potential of flk2/flt3+ multipotent hematopoietic progenitors. Cell. 2006 Jul 28;126(2):415-26.
• Forsberg EC, Prohaska SS, Katzman S, Heffner GC, Stuart JM, Weissman IL. Differential expression of novel potential regulators in hematopoietic stem cells. PLoS Genet. 2005 Sep;1(3):e28.