Stem Cell Program Labs

The Daley Lab

The Daley laboratory focuses on stem cell biology, with an emphasis on hematopoietic differentiation from human and mouse embryonic stem cells (ES cells), cellular reprogramming, germ cell development, human disease modeling, and the study of the BCR-ABL oncoprotein of chronic myeloid leukemia, the classic malignancy of hematopoietic stem cells (HSCs). Our primary research areas are:

    • Directed differentiation of Hematopoietic Stem Cells (HSCs) from pluripotent cells: Mechanisms of directed blood differentiation and models for functional hematopoietic engraftment in diseased animals remain poorly defined. We study hematopoietic development in mouse embryos and differentiating cultures of human and mouse pluripotent stem cells to define the molecular genetic programs that enable formation of HSCs in experimental and therapeutic models.
    • Cellular reprogramming: Our laboratory was among the first three groups in the world to show that mature cells obtained from a patient’s biopsy are capable of being reprogrammed to an embryonic-like state. We are currently using these induced pluripotent stem cells to advance our understanding of congenital and acquired diseases, with an ultimate goal of creating patient-matched cells for transplantation therapy.
    • Elucidation of pathways of oncogenesis: We study pathways that promote malignant transformation of cells, especially pertaining to pathways common to cancer and tissue stem cells. Of particular interest in the oncoprotein LIN28, which regulates the biogenesis of the let-7 family of tumor suppressor microRNAs.

    For a virtual tour of the Daley lab, please view our video.

    SELECTED REFERENCES

    Kim K, Lerou P, Yabuuchi A, Lengerke C, Ng K, West J, Kirby A, Daly M, Daley GQ. Histocompatible embryonic stem cells by parthenogenesis. Science 2007 315(5811):482-6. Epub 2006 Dec 14; PMID: 17170255.

    Park I-H, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, and Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008 451(7175):141-6. Epub 2007 Dec 23; PMID: 18157115.

    Park I-H, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-specific induced pluripotent stem cells. Cell 2008 134(5):877-86. Epub 2008 Aug 7; PMID: 18691744; PMCID: PMC2633781.

    Adamo L, Naveiras O, McKinney-Freeman S, Mack PJ, Suchy-Dicey A, Yoshimoto M, Lensch MW, Yoder MC, García-Cardeña G, Daley GQ. Biomechanical forces promote embryonic hematopoiesis. Nature 2009 Jun 25;459(7250):1131-5. Epub 2009 May 13; PMID: 19440194.

    Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone Marrow Adipocytes as Negative Regulators of the Hematopoietic Microenvironment. Nature 2009 Jul 9;460(7252):259-63. Epub 2009 Jun 10; PMID: 19516257.

    West J, Viswanathan SR, Yabuuchi A, Takeuchi A, Cunniff K, Park IH, Sero JE, Perez-Atayde A, Frazier AL, Surani MA, Daley GQ. A role for Lin28 in germ cell development and germ cell malignancy. Nature 2009 460(7257):909-13; online July 5; PMID: 19578360; PMCID: PMC2729657.

    Agarwal S, Loh Y-H, McLoughlin EM, Huang J, Park I-H, Miller JD, Huo H, Rosana Okuka M, Maria dos Reis RM, Loewer S, Ng, H-H, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, and Daley GQ. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 2010 online Feb 17; PMID: 20164838.

    Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich L, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, Mckinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, and Daley GQ. Epigenetic memory in induced pluripotent stem cells. Nature 2010 467(7313):285-90. Epub July 19. PMID: 20644535.

    Zhu H, Shyh-Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI; DIAGRAM Consortium; MAGIC Investigators, Altshuler D, Daley GQ. The Lin28/let-7 axis regulates glucose metabolism. Cell. 2011 147; 81-94 Sept 30 doi:10.1016/j.cell.2011.08.033.PMID: 31962509.

    Onder TT, Kara N, Cherry ABC, Sinha AU, Zhu N, Bernt KM, Cahan P, Mancarci OB, Unternaehrer J, Gupta PB, Lander ES, Armstrong SA, Daley GQ. Chromatin modifying enzymes as modulators of reprogramming. Nature. 2012 Mar 4;483(7391):598-602. doi: 10.1038/nature10953. PMID: 22388813.

    Shyh-Chang N, Zhu H, Yvanka de Soysa T, Shinoda G, Seligson MT, Tsanov KM, Nguyen L, Asara JM, Cantley LC, Daley GQ. Lin28 enhances tissue repair by reprogramming cellular metabolism. Cell 2013 Nov 7;155(4):778-92. doi: 10.1016/j.cell.2013.09.059. PMID: 24209617.

    Morris SA, Cahan P, Li H, Lu Y-F, Zhao AM, Sahalie J, San Roman AK, Shivdasani RA, Collins JJ, Daley GQ. Enhancing cellular engineering through network biology. Cell 2014 Aug 14;158(4):889-902. doi: 10.1016/j.cell.2014.07.021. PMID:25126792.

    Powers JT, Tsanov KM, Pearson DS, Roels F, Spina CS, Ebright R, Seligson M, de Soysa Y, Cahan P, Theißen J, Tu HC, Han A, LaPier GS, Kurek KC, Osborne JK, Ross SJ, Cesana M, Collins JJ, Berthold F, Daley GQ. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. Nature 2016 Jul 6;535(7611):246-51. doi: 10.1038/nature18632. PMID:27383785

    Sugimura R, Jha DK, Han A, Soria-Valles C, da Rocha EL, Lu Y-F, Goettel JA, Serrao E, Rowe RG, Malleshaiah M, Wong I, Sousa P, Zhu TN, Ditadi A, Keller G, Engelman AN, Snapper SB, Doulatov S, and Daley GQ. Hematopoietic stem and progenitor cells from human pluripotent stem cells. Nature. 2017 May 25;545(7655):432-438. doi: 10.1038/nature22370. Epub 2017 May 17. PMID: 28514439

    Vo LT, Kinney MA, Liu X, Zhang Y, Barragan J, Sousa PM, Jha DK, Han A, Cesana M, Shai Z, North TE, Orkin SH, Doulatov S, Xu J, and Daley GQ. Regulation of haematopoietic multipotency by EZH1. Nature (in press).

Giving

Spotlight

  • Embryonic stem cells teach lessons about Fanconi anemia

    Children with Fanconi anemia, a rare genetic disease, often begin experiencing low blood cell counts at about age 7, and can die unless they get a bone marrow transplant. Now, by modeling Fanconi anemia in the lab using human ES cells, researchers at Children’s Hospital Boston reveal that inadequate production of blood cells may actually begin long before birth, casting a whole new light on the disease. ES cells were used because past research has shown Fanconi anemia to be difficult to model with induced pluripotent cells
    . Read more.