Christopher M. Sturgeon, Ph.D.

Assistant Professor
Internal Medicine
Hematology
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program

  • 314-362-8893

  • 8125

  • csturgeon@wustl.edu

  • www.sturgeonlab.com

  • stem cell, embryonic, iPSC, hematopoiesis, HSC, hESC, development

  • Regulation of human hematopoietic development

Research Abstract:

The directed differentiation of human pluripotent stem cells (hPSC) towards the hematopoietic lineages would be an invaluable tool for regenerative medicine, providing cells for both transplantation and in vitro analysis. As the PSC system has been shown to recapitulate developmental events in vitro, it is also a powerful model system for developmental biology, being the only method to-date that allows interrogation of the cellular and molecular mechanisms that regulate human development. Furthermore, the recent technological advancement to generate induced pluripotent stem cells offers the potential to model not only development, but also disease in a dish.

Current efforts to generate an hPSC-derived hematopoietic stem cell (HSC) are plagued by an inability to accurately discriminate between progenitors of the primitive and definitive hematopoietic programs, as there is no anatomical separation between the two in vitro. Briefly, very early in embryonic development the primitive hematopoietic program gives rise to a subset of lineages, including unique erythroblasts with high oxygen-affinity hemoglobin to promote embryonic survival, but no T cells or hematopoietic stem cells. This program is transient, and is shut down prior to the intra-embryonic emergence of the definitive hematopoietic program, which generates the full spectrum of hematopoietic lineages, including T cells and the hematopoietic stem cell. Both programs appear to progress in a similar fashion, passing through a mesodermal precursor and then subsequent hemogenic endothelium. However, as only the definitive program gives rise to a bona fide HSC, understanding the mechanism(s) that control specification of this program are essential to achieving this goal.

The focus of my lab is to elucidate the signaling pathways governing the specification of both hematopoietic programs using hPSC directed differentiation. Through this we aim to better understand the transcriptional and epigenetic regulation that controls HSC development, and identify method(s) to specify a transplantable HSC in the dish. Work in my laboratory is focused on three main objectives:

Understanding human primitive and definitive hematopoietic development

Understanding the endothelial-to-hematopoietic transition in hemogenic endothelium, ultimately giving rise to an HSC

Modeling hematopoietic disease with iPSC

Selected Publications:

Fok WC, Niero ELO, Dege C, Brenner KA, Sturgeon CM*, Batista LFZ*. p53 Mediates Failure of Human Definitive Hematopoiesis in Dyskeratosis Congenita. Stem Cell Reports. 2017 Aug 8;9(2):409-418.

Creamer JP, Dege C, Ren Q, Ho JTK, Valentine MC, Druley TE, Sturgeon CM. Human definitive hematopoietic specification from pluripotent stem cells is regulated by mesodermal expression of CDX4. Blood. 2017 Jun 1;129(22):2988-2992.

Ditadi A, Sturgeon CM. Directed differentiation of definitive hemogenic endothelium and hematopoietic progenitors from human pluripotent stem cells. Methods. 2016 May 15;101:65-72.

Ditadi A, Sturgeon CM, Tober J, Awong G, Kennedy M, Yzaguirre AD, Azzola L, Ng ES, Stanley EG, French DL, Cheng X, Gadue P, Speck NA, Elefanty AG, Keller G. Human definitive haemogenic endothelium and arterial vascular endothelium represent distinct lineages. Nature Cell Biology. 2015 May;17(5):580-91

Sturgeon CM, Ditadi A, Awong G, Kennedy M, Keller G. Wnt Signaling Controls the Specification of
Definitive and Primitive Hematopoiesis From Human Pluripotent Stem Cells. Nature Biotechnology. 2014 32(6):554-561

Sturgeon CM, Ditadi A, Clarke RL, Keller G. Defining the path to hematopoietic stem cells. Nature Biotechnology. 2013 31:416-418

Kennedy M*, Awong G*, Sturgeon CM, Ditadi A, LaMotte-Mohs , R., Ziga-Pflcker, J.C., Keller G. T cell potential defines definitive hematopoiesis in hESC differentiation cultures. Cell Reports. 2012 2(6):1722-35

Sturgeon CM, Chicha L, Ditadi A, Zhou Q, McGrath KE, Palis J, Hammond SM, Wang S, Olson EN, Keller G. Primitive erythropoiesis is regulated by miR-126 via non-hematopoietic Vcam-1+ cells. Developmental Cell. 2012 23(1):45-57

Last Updated: 7/25/2018 8:16:24 AM

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