Information

Related Research Units

Dana Farber Boston Childrens Cancer and Blood Disorders Center Research
Hematology and Oncology Research
Trista North Lab Research

Research Overview

Assistant's information - Aubrey Plumb, aubrey.plumb@childrens.harvard.edu

Hematopoietic stem cells (HSCs) form the base of the hematopoietic hierarchy and can give rise to each of the blood lineages present during a vertebrate’s lifetime. Gene programs and signaling networks regulating HSC development and function are highly evolutionarily conserved, with dysregulation resulting in blood disorders and malignancies. HSCs are therapeutically valuable for the treatment of hematologic disease, but are in limited supply and currently cannot be effectively expanded or produced in vitro. My research utilizes genetic methods and chemical biology approaches in the zebrafish embryo to identify and characterize pathways regulating HSC induction, self-renewal and lineage commitment in vivo. To demonstrate regulatory conservation and translational application, we employ in vivo functional analyses in adult zebrafish and mice, as well as human in vitro hematopoietic differentiation assays. Through these efforts, we have uncovered a series of extrinsic or environmental cues that influence the spatio-temporal development, expansion and maintenance of HSCs across vertebrates, which has direct translational relevance for the de novo derivation of HSCs for therapeutic application.

Research Background

Dr. Trista E. North is a Professor of Pediatrics of Pediatrics at Harvard Medical School, principle investigator in the Stem Cell Program and Department of Hematology/Oncology at Boston Children’s Hospital and Co-Director of the Developmental and Regenerative Biology graduate program. Dr. North received her BA from Bowdoin College in 1996, and PhD from Dartmouth College in 2002. Following completion of her postdoctoral research at Boston Children’s Hospital, Dr. North established her independent research laboratory in 2008 with a focus on Developmental Hematopoiesis. She is an active faculty member in the Biological and Biomedical Sciences Graduate Program at HMS, the Harvard Stem Cell Institute, and Dana-Farber/Harvard Cancer Center Leukemia Program. Dr. North currently serves as Treasurer on the Executive Board of the Zebrafish Disease Models Society; she is also a member of the Stem Cells and Regenerative Medicine Scientific Committee of the American Society of Hematology, and Nominating Committee for the International Society of Experimental Hematology.

Publications

  1. Maturation and persistence of CAR T cells derived from human pluripotent stem cells via chemical inhibition of G9a/GLP. Cell Stem Cell. 2025 Jan 15. View Abstract
  2. Maturation and persistence of CAR T cells derived from human pluripotent stem cells via chemical inhibition of G9a/GLP. Cell Stem Cell. 2025 Jan 02; 32(1):71-85.e5. View Abstract
  3. Bnip3lb-driven mitophagy sustains expansion of the embryonic hematopoietic stem cell pool. bioRxiv. 2024 Sep 23. View Abstract
  4. Correction: Cannabinoid receptor signaling regulates liver development and metabolism. Development. 2024 Aug 01; 151(15). View Abstract
  5. A multistep computational approach reveals a neuro-mesenchymal cell population in the embryonic hematopoietic stem cell niche. Development. 2024 Apr 01; 151(7). View Abstract
  6. Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. Cell Stem Cell. 2023 11 02; 30(11):1434-1451.e9. View Abstract
  7. SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function. Hepatol Commun. 2023 11 01; 7(11). View Abstract
  8. Structural basis for inactivation of PRC2 by G-quadruplex RNA. Science. 2023 09 22; 381(6664):1331-1337. View Abstract
  9. Embryonic alcohol exposure disrupts the ubiquitin-proteasome system. JCI Insight. 2022 12 08; 7(23). View Abstract
  10. EZH1 repression generates mature iPSC-derived CAR T cells with enhanced antitumor activity. Cell Stem Cell. 2022 08 04; 29(8):1181-1196.e6. View Abstract
  11. Hypoxic, glycolytic metabolism is a vulnerability of B-acute lymphoblastic leukemia-initiating cells. Cell Rep. 2022 04 26; 39(4):110752. View Abstract
  12. CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development. Nat Cell Biol. 2022 04; 24(4):579-589. View Abstract
  13. Developmental maturation of the hematopoietic system controlled by a Lin28b-let-7-Cbx2 axis. Cell Rep. 2022 04 05; 39(1):110587. View Abstract
  14. Making Blood from the Vessel: Extrinsic and Environmental Cues Guiding the Endothelial-to-Hematopoietic Transition. Life (Basel). 2021 Sep 29; 11(10). View Abstract
  15. Lin28 paralogs regulate lung branching morphogenesis. Cell Rep. 2021 07 20; 36(3):109408. View Abstract
  16. Sequential regulation of hemogenic fate and hematopoietic stem and progenitor cell formation from arterial endothelium by Ezh1/2. Stem Cell Reports. 2021 07 13; 16(7):1718-1734. View Abstract
  17. Ddx41 loss R-loops in cGAS to fuel inflammatory HSPC production. Dev Cell. 2021 03 08; 56(5):571-572. View Abstract
  18. Estrogen Acts Through Estrogen Receptor 2b to Regulate Hepatobiliary Fate During Vertebrate Development. Hepatology. 2020 11; 72(5):1786-1799. View Abstract
  19. An induced pluripotent stem cell model of Fanconi anemia reveals mechanisms of p53-driven progenitor cell differentiation. Blood Adv. 2020 10 13; 4(19):4679-4692. View Abstract
  20. Metabolic Regulation of Inflammasome Activity Controls Embryonic Hematopoietic Stem and Progenitor Cell Production. Dev Cell. 2020 10 26; 55(2):133-149.e6. View Abstract
  21. Transcriptome Dynamics of Hematopoietic Stem Cell Formation Revealed Using a Combinatorial Runx1 and Ly6a Reporter System. Stem Cell Reports. 2020 05 12; 14(5):956-971. View Abstract
  22. YAP Regulates Hematopoietic Stem Cell Formation in Response to the Biomechanical Forces of Blood Flow. Dev Cell. 2020 02 24; 52(4):446-460.e5. View Abstract
  23. Author Correction: A systems biology pipeline identifies regulatory networks for stem cell engineering. Nat Biotechnol. 2019 Aug; 37(8):962. View Abstract
  24. A systems biology pipeline identifies regulatory networks for stem cell engineering. Nat Biotechnol. 2019 07; 37(7):810-818. View Abstract
  25. The developmental stage of the hematopoietic niche regulates lineage in MLL-rearranged leukemia. J Exp Med. 2019 03 04; 216(3):527-538. View Abstract
  26. Estrogen Activation of G-Protein-Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes. Gastroenterology. 2019 05; 156(6):1788-1804.e13. View Abstract
  27. Reconstruction of complex single-cell trajectories using CellRouter. Nat Commun. 2018 03 01; 9(1):892. View Abstract
  28. Regulation of embryonic haematopoietic multipotency by EZH1. Nature. 2018 01 25; 553(7689):506-510. View Abstract
  29. A tool compound targeting the core binding factor Runt domain to disrupt binding to CBFß in leukemic cells. Leuk Lymphoma. 2018 09; 59(9):2188-2200. View Abstract
  30. Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization. Stem Cell Reports. 2017 05 09; 8(5):1226-1241. View Abstract
  31. Netting Novel Regulators of Hematopoiesis and Hematologic Malignancies in Zebrafish. Curr Top Dev Biol. 2017; 124:125-160. View Abstract
  32. Haematopoietic stem cells show their true colours. Nat Cell Biol. 2016 Dec 23; 19(1):10-12. View Abstract
  33. Hematopoietic stem cell development: Using the zebrafish to identify extrinsic and intrinsic mechanisms regulating hematopoiesis. Methods Cell Biol. 2017; 138:165-192. View Abstract
  34. HIF1a-induced PDGFRß signaling promotes developmental HSC production via IL-6 activation. Exp Hematol. 2017 Feb; 46:83-95.e6. View Abstract
  35. Developmental Vitamin D Availability Impacts Hematopoietic Stem Cell Production. Cell Rep. 2016 10 04; 17(2):458-468. View Abstract
  36. Evi1 regulates Notch activation to induce zebrafish hematopoietic stem cell emergence. EMBO J. 2016 11 02; 35(21):2315-2331. View Abstract
  37. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development. Dev Biol. 2016 10 01; 418(1):108-123. View Abstract
  38. Inflammatory signals in HSPC development and homeostasis: Too much of a good thing? Exp Hematol. 2016 10; 44(10):908-12. View Abstract
  39. The Central Nervous System Regulates Embryonic HSPC Production via Stress-Responsive Glucocorticoid Receptor Signaling. Cell Stem Cell. 2016 09 01; 19(3):370-82. View Abstract
  40. Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish. J Exp Med. 2016 05 30; 213(6):979-92. View Abstract
  41. EnaBILEing Growth in the Fetal Liver. Cell Stem Cell. 2016 Apr 07; 18(4):427-8. View Abstract
  42. Endothelial-to-hematopoietic transition: Notch-ing vessels into blood. Ann N Y Acad Sci. 2016 04; 1370(1):97-108. View Abstract
  43. Cannabinoid receptor signaling regulates liver development and metabolism. Development. 2016 Feb 15; 143(4):609-22. View Abstract
  44. Enumerating Hematopoietic Stem and Progenitor Cells in Zebrafish Embryos. Methods Mol Biol. 2016; 1451:191-206. View Abstract
  45. Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation. Stem Cell Reports. 2015 Oct 13; 5(4):471-9. View Abstract
  46. Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via Prostaglandin E2 and P-Selectin Activity. Stem Cells. 2015 Aug; 33(8):2596-612. View Abstract
  47. Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production. Genes Dev. 2014 Dec 01; 28(23):2597-612. View Abstract
  48. Repairing quite swimmingly: advances in regenerative medicine using zebrafish. Dis Model Mech. 2014 Jul; 7(7):769-76. View Abstract
  49. Estrogen defines the dorsal-ventral limit of VEGF regulation to specify the location of the hemogenic endothelial niche. Dev Cell. 2014 May 27; 29(4):437-53. View Abstract
  50. Oceans of opportunity: exploring vertebrate hematopoiesis in zebrafish. Exp Hematol. 2014 Aug; 42(8):684-96. View Abstract
  51. Prostaglandin E2 regulates liver versus pancreas cell-fate decisions and endodermal outgrowth. Dev Cell. 2014 Feb 24; 28(4):423-37. View Abstract
  52. S-nitrosothiol signaling regulates liver development and improves outcome following toxic liver injury. Cell Rep. 2014 Jan 16; 6(1):56-69. View Abstract
  53. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood. 2013 Oct 24; 122(17):3074-81. View Abstract
  54. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development. Dis Model Mech. 2013 Sep; 6(5):1271-8. View Abstract
  55. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol. 2013 Aug; 9(8):514-20. View Abstract
  56. Glucose metabolism impacts the spatiotemporal onset and magnitude of HSC induction in vivo. Blood. 2013 Mar 28; 121(13):2483-93. View Abstract
  57. Rargb regulates organ laterality in a zebrafish model of right atrial isomerism. Dev Biol. 2012 Dec 15; 372(2):178-89. View Abstract
  58. Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis. Dev Biol. 2013 Jan 15; 373(2):431-41. View Abstract
  59. SCF(ß-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. J Exp Med. 2012 Jul 02; 209(7):1289-307. View Abstract
  60. Mutation mapping and identification by whole-genome sequencing. Genome Res. 2012 Aug; 22(8):1541-8. View Abstract
  61. Small molecule screening identifies targetable zebrafish pigmentation pathways. Pigment Cell Melanoma Res. 2012 Mar; 25(2):131-43. View Abstract
  62. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell. 2011 Apr 08; 8(4):445-58. View Abstract
  63. Endoderm specification, liver development, and regeneration. Methods Cell Biol. 2011; 101:205-23. View Abstract
  64. Hematopoietic stem cell development: using the zebrafish to identify the signaling networks and physical forces regulating hematopoiesis. Methods Cell Biol. 2011; 105:117-36. View Abstract
  65. PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proc Natl Acad Sci U S A. 2010 Oct 05; 107(40):17315-20. View Abstract
  66. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science. 2010 Mar 26; 327(5973):1650-3. View Abstract
  67. Previews. NOTCHing an arrow at cord blood: translating stem cell knowledge into clinical practice. Cell Stem Cell. 2010 Mar 05; 6(3):186-7. View Abstract
  68. Hematopoietic stem cell development is dependent on blood flow. Cell. 2009 May 15; 137(4):736-48. View Abstract
  69. Topoisomerase II alpha is required for embryonic development and liver regeneration in zebrafish. Mol Cell Biol. 2009 Jul; 29(13):3746-53. View Abstract
  70. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009 Mar 20; 136(6):1136-47. View Abstract
  71. Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling. Oncogene. 2008 Oct 02; 27(44):5845-55. View Abstract
  72. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. Dev Biol. 2008 Aug 01; 320(1):161-74. View Abstract
  73. Prostaglandin E2: making more of your marrow. Cell Cycle. 2007 Dec 15; 6(24):3054-7. View Abstract
  74. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature. 2007 Jun 21; 447(7147):1007-11. View Abstract
  75. Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors. Nat Methods. 2007 Jul; 4(7):551-3. View Abstract
  76. New waves of discovery: modeling cancer in zebrafish. J Clin Oncol. 2007 Jun 10; 25(17):2473-9. View Abstract
  77. Runx1 is expressed in adult mouse hematopoietic stem cells and differentiating myeloid and lymphoid cells, but not in maturing erythroid cells. Stem Cells. 2004; 22(2):158-68. View Abstract
  78. Modeling human hematopoietic and cardiovascular diseases in zebrafish. Dev Dyn. 2003 Nov; 228(3):568-83. View Abstract
  79. Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity. 2002 May; 16(5):661-72. View Abstract
  80. Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development. 1999 Jun; 126(11):2563-75. View Abstract
  81. Core-binding factor: a central player in hematopoiesis and leukemia. Cancer Res. 1999 Apr 01; 59(7 Suppl):1789s-1793s. View Abstract

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