**Authors in BOLD denote Spence Lab members  // Spence Lab publications in PubMed                                                                


We deposit all of our manuscripts as preprints - check out our latest work here:


PEG-4MAL hydrogels for human organoid generation, culture, and in vivo delivery. Cruz-Acuña R, Quirós M, Huang S, Siuda D, Spence JR***, Nusrat A***, García AJ***. Nat Protoc. 2018 Sep;13(9):2102-2119. doi: 10.1038/s41596-018-0036-3. Erratum in: Nat Protoc. 2018 Oct 24;:. PMID: 30190557 ***co-senior/corresponding authors

Single-cell analysis of progenitor cell dynamics and lineage specification in the human fetal kidney. Menon R, Otto EA, Kokoruda A, Zhou J, Zhang Z, Yoon E, Chen YC, Troyanskaya O, Spence JR***, Kretzler M***, Cebrián C***. Development. 2018 Aug 30;145(16). pii: dev164038. doi: 10.1242/dev.164038. PMID:30166318  ***co-senior/corresponding authors

Lactobacillus rhamnosus GG prevents epithelial barrier dysfunction induced by interferon-gamma and fecal supernatants from irritable bowel syndrome patients in human intestinal enteroids and colonoids Han X, Lee A, Huang S, Gao J, Spence JR, Owyang C. Gut Microbes. 2018 Jul 24:1-18. doi: 10.1080/19490976.2018.1479625. PMID:30040527

A Method for Cryogenic Preservation of Human Biopsy Specimens and Subsequent Organoid Culture. Tsai YH***, Czerwinski M***, Wu A, Dame MK, Attili D, Hill E, Colacino JA, Nowacki LM, Shroyer NF, Higgins PDR, Kao JY, Spence JR. Cell Mol Gastroenterol Hepatol. 2018 May 30;6(2):218-222.e7. doi: 10.1016/j.jcmgh.2018.04.008. eCollection 2018.  PMID:30105282  ***=co-first authors/equal contribution

Taming the Wild West of Organoids, Enteroids, and Mini-Guts. Spence JR. Cell Mol Gastroenterol Hepatol. 2017 Nov 28;5(2):159-160. doi: 10.1016/j.jcmgh.2017.11.003. eCollection 2018. No abstract available. PMID:29693042  *Invited Commentary

Identification, Isolation, and Characterization of Human LGR5-positive Colon Adenoma Cells  Dame MK, Attili D, McClintock SD, Dedhia PH, Ouillette P, Hardt O, Chin AM, Xue X, Laliberte J, Katz EL, Newsome GM, Hill DR, Miller AJ, Tsai YH, Agorku D, Altheim CH, Bosio A, Simon B, Samuelson LC, Stoerker JA, Appelman HD, Varani J, Wicha MS, Brenner DE, Shah YM, Spence JR, Colacino JA. Development. 2018 Mar 14;145(6). pii: dev153049. doi: 10.1242/dev.153049.  PMID:29467240

In Vitro Induction and In Vivo Engraftment of Lung Bud Tip Progenitor Cells Derived from Human Pluripotent Stem Cells. Miller AJ, Hill DR, Nagy MS, Aoki Y, Dye BR, Chin AM, Huang S, Zhu F, White ES, Lama V, Spence JR. Stem Cell Reports. 2017 Dec 12. pii: S2213-6711(17)30519-2. doi: 10.1016/j.stemcr.2017.11.012. [Epub ahead of print] PMID:29249664


Real-time Measurement of Epithelial Barrier Permeability in Human Intestinal Organoids. Hill, D.R., Huang, S., Tsai, Y.H., Spence, J.R., Young, V.B. J. Vis. Exp. (), e56960, doi:10.3791/56960 (2017).  VIDEO HERE   PDF HERE

Clocking the Pace of Organoid Research. Spence JR. Cell Mol Gastroenterol Hepatol. 2017 May 13;4(1):203-204. doi: 10.1016/j.jcmgh.2017.04.006. eCollection 2017 Jul. No abstract available. PMID:29204507 *invited comentary

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium. Hill DR, Huang S, Nagy MS, Yadagiri VK, Fields C, Mukherjee D, Bons B, Dedhia PH, Chin AM, Tsai YH, Thodla S, Schmidt TM, Walk S, Young VB*, Spence JR*. Elife. 2017 Nov 7;6. pii: e29132. doi: 10.7554/eLife.29132.  PMID:29110754 * co-corresponding/senior authors

Synthetic hydrogels for human intestinal organoid generation and colonic wound repair. Cruz-Acuña R^, Quirós M^, Farkas AE, Dedhia PH, Huang S, Siuda D, García-Hernández V, Miller AJ, Spence JR**, Nusrat A**, García AJ**. Nature Cell Biology. 2017. published ahead of print October 23. doi: https://doi.org/10.1038/ncb3632  ^co-first authors; **co-corresponding/senior authors PDF HERE

Quantitative proteomics identifies STEAP4 as a critical regulator of mitochondrial dysfunction linking inflammation and colon cancer.  Xue X, Bredell BX, Anderson ER, Martin A, Mays C, Nagao-Kitamoto H, Huang S, Győrffy B, Greenson JK, Hardiman K, Spence JR, Kamada N, Shah YM.  Proceedings of the National Academy of Sciences. 2017. published ahead of print October 23, 2017, doi:10.1073/pnas.1712946114

Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems.   Dye BR, Kasputis T, Spence JR and  Shea LD.  MRS Communications. Volume 7, Issue 3 September 2017 , pp. 502-514. Review.  https://doi.org/10.1557/mrc.2017.61

Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling. Quiros M, Nishio H, Neumann PA, Siuda D, Brazil JC, Azcutia V, Hilgarth R, O'Leary MN, Garcia-Hernandez V, Leoni G, Feng M, Bernal G, Williams H, Dedhia PH, Gerner-Smidt C, Spence J, Parkos CA, Denning TL, Nusrat A. J Clin Invest. 2017 Sep 1;127(9):3510-3520. doi: 10.1172/JCI90229. Epub 2017 Aug 7. PMID:28783045

Neural Crest Cell Implantation Restores Enteric Nervous System Function and Alters the Gastrointestinal Transcriptome in Human Tissue-Engineered Small Intestine. Schlieve CR, Fowler KL, Thornton M, Huang S, Hajjali I, Hou X, Grubbs B, Spence JR, Grikscheit TC. Stem Cell Reports. 2017 Aug 9. pii: S2213-6711(17)30327-2. doi: 10.1016/j.stemcr.2017.07.017. [Epub ahead of print] PMID:28803915

In Vitro Models to Study Human Lung Development, Disease and Homeostasis. Miller AJSpence JR. Physiology (Bethesda). 2017 May;32(3):246-260. doi: 10.1152/physiol.00041.2016. Review. PMID:28404740

Differentiation of Human Pluripotent Stem Cells into Colonic Organoids via Transient Activation of BMP Signaling. Múnera JO, Sundaram N, Rankin SA, Hill DR, Watson C, Mahe M, Vallance JE, Shroyer NF, Sinagoga KL, Zarzoso-Lacoste A, Hudson JR, Howell JC, Chatuvedi P, Spence JR, Shannon JM, Zorn AM, Helmrath MA, Wells JM. Cell Stem Cell. 2017 Jul 6;21(1):51-64.e6. doi: 10.1016/j.stem.2017.05.020. Epub 2017 Jun 22. PMID:28648364

Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche. Shao Y, Taniguchi K, Gurdziel K, Townshend RF, Xue X, Yong KM, Sang J, Spence JR, Gumucio DL, Fu J. Nat Mater. 2017 Apr;16(4):419-425. doi: 10.1038/nmat4829. Epub 2016 Dec 12. PMID:27941807

Bioengineering for intestinal organoid cultures. Kim GA, Spence JR, Takayama S. Curr Opin Biotechnol. 2017 Jun 21;47:51-58. doi: 10.1016/j.copbio.2017.05.006. [Epub ahead of print] Review. PMID:28646678

Notch1 and Notch2 receptors regulate mouse and human gastric antral epithelial cell homoeostasis. Gifford GB, Demitrack ES, Keeley TM, Tam A, La Cunza N, Dedhia PH, Spence JR, Simeone DM, Saotome I, Louvi A, Siebel CW, Samuelson LC. Gut. 2017 Jun;66(6):1001-1011. doi: 10.1136/gutjnl-2015-310811. Epub 2016 Mar 1. PMID: 26933171

Morphogenesis and maturation of the embryonic and postnatal intestine. Chin AM, Hill DR, Aurora M, Spence JR.   Semin Cell Dev Biol. 2017 Feb 1. pii: S1084-9521(17)30066-6. doi: 10.1016/j.semcdb.2017.01.011.

In vitro patterning of pluripotent stem cell-derived intestine recapitulates in vivo human development.  Tsai YH* and Nattiv R*, Dedhia PH, Nagy MS, Chin AM,  Thomson M, Klein OD, Spence JR. Development. 2017 Mar 15;144(6):1045-1055. doi: 10.1242/dev.138453.    *equal contribution

(Re)Building a Kidney.  Leif Oxburgh, Thomas J. Carroll, Ondine Cleaver, Daniel R. Gossett, Deborah K. Hoshizaki, Jeffrey A. Hubbell,  Benjamin D. Humphreys, Sanjay Jain, Jan Jensen, David L. Kaplan, Carl Kesselman, Christian J. Ketchum, Melissa H. Little, Andrew P. McMahon, Stuart J. Shankland,  Jason R. Spence, M. Todd Valerius, Jason A. Wertheim, Oliver Wessely, Ying Zheng, and Iain A. Drummond.  J Am Soc Nephrol  http://jasn.asnjournals.org/content/early/2017/01/16/ASN.2016101077.full

BRAFV600E cooperates with CDX2 inactivation to promote serrated colorectal tumorigenesis. Sakamoto N, Feng Y, Stolfi C, Kurosu Y, Green M, Lin J, Green M, Sentani K, Yasui W, McMahon M, Hardiman KM, Spence JR, Horita N, Greenson JK, Kuick R, Cho KR, Fearon ER. Elife. 2017 Jan 10;6. pii: e20331. doi: 10.7554/eLife.20331.

Hacking the Matrix. Czerwinski MSpence JR. Cell Stem Cell. 2017 Jan 5;20(1):9-10. doi: 10.1016/j.stem.2016.12.010. *invited commentary


Gastrointestinal organoids: understanding the molecular basis of the host-microbe interface Hill DR and Spence JR  Cell Mol Gastroenterol Hepatol. 2016 Dec 19;3(2):138-149. doi: 10.1016/j.jcmgh.2016.11.007. Review.  PMID:28275681

A Dynamic WNT/β-CATENIN Signaling Environment Leads to WNT-Independent and WNT-Dependent Proliferation of Embryonic Intestinal Progenitor Cells. Chin AM, Tsai YH, Finkbeiner SR, Nagy MS, Walker EM, Ethen NJ, Williams BO, Battle MA, Spence JR. Stem Cell Reports. 2016 Oct 6. pii: S2213-6711(16)30210-7. doi: 10.1016/j.stemcr.2016.09.004.

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. Dye BR, Dedhia PH, Miller AJ, Nagy MS, White ES, Shea LD, Spence JR. Elife. 2016 Sep 28;5. pii: e19732. doi: 10.7554/eLife.19732. [Epub ahead of print]

LGR4 and LGR5 Function Redundantly During Human Endoderm DifferentiationTsai YH, Hill DR, Kumar N, Huang S, Chin AM, Dye BR, Nagy MS, Verzi MP, Spence JR.  Cell Mol Gastroenterol Hepatol. 2016 Jun 23;2(5):648-662.e8. DOI: http://dx.doi.org/10.1016/j.jcmgh.2016.06.002

Hox6 genes modulate in vitro differentiation of mESCs to insulin-producing cells. Larsen BM, Marty-Santos L, Newman M, Lukacs DT, Spence JR, Wellik DM. In Vitro Cell Dev Biol Anim. 2016 Jul 21. [Epub ahead of print] PMID:27444630

hPSC-derived lung and intestinal organoids as models of human fetal tissue. Aurora M, Spence JR. Dev Biol. 2016 Jun 7. pii: S0012-1606(16)30188-9. doi: 10.1016/j.ydbio.2016.06.006. [Epub ahead of print] Review. PMID:27287882

How to grow a lung: Applying Principles of Developmental Biology to Generate Lung Lineages From Human Pluripotent Stem Cells. Dye BR, Miller AJ, Spence JR. Current Pathobiology Reports. June 2016, Volume 4, Issue 2, pp 47–57

Organoid Models of Human Gastrointestinal Development and Disease. Dedhia PH, Bertaux-Skeirik N, Zavros Y, Spence JR. Gastroenterology. 2016 Jan 13. doi: 10.1053/j.gastro.2015.12.042. [Epub ahead of print] Review. PMID: 26774180


Lumen Formation Is an Intrinsic Property of Isolated Human Pluripotent Stem Cells. Taniguchi K, Shao Y, Townshend RF, Tsai YH, DeLong CJ, Lopez SA, Gayen S, Freddo AM, Chue DJ, Thomas DJ, Spence JR, Margolis B, Kalantry S, Fu J, O'Shea KS, Gumucio DL. Stem Cell Reports. 2015 Nov 24. pii: S2213-6711(15)00312-4.  PMID:26626176

Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoidsFinkbeiner SR, Freeman JJ,  Wieck MM,  El-Nachef W,  Altheim CH, Tsai YH, Huang S, Dyal R, White ES, Grikscheit TC, Teitelbaum DH, Spence JR. Biol Open. 2015 Oct 12;4(11):1462-72.  PMID:26459240 http://dx.doi.org/10.1242/bio.013235

Hox5 Genes Regulate the Wnt2/2b-Bmp4-Signaling Axis during Lung Development. Hrycaj SM, Dye BR, Baker NC, Larsen BM, Burke AC, Spence JR, Wellik DM. Cell Rep. 2015 Aug 11;12(6):903-12.  PMID: 26235626

Transcriptome-wide Analysis Reveals Hallmarks of Human Intestine Development and Maturation In Vitro and In Vivo. Finkbeiner SR, Hill DR, Altheim CH, Dedhia PH, Taylor MJ, Tsai YH, Chin AM, Mahe MM, Watson CL, Freeman JJ, Nattiv R, Thomson M, Klein OD, Shroyer NF, Helmrath MA, Teitelbaum DH, Dempsey PJ, Spence JR. Stem Cell Reports. 2015 Jun 3  PMID:26050928

Intestinal organoids: A model of intestinal fibrosis for evaluating anti-fibrotic drugs. Rodansky ES, Johnson LA, Huang S, Spence JR, Higgins PD. Exp Mol Pathol. 2015 Mar 28. PMID: 25828392

In vitro generation of human pluripotent stem cell derived lung organoids. Dye BR, Hill DR, Ferguson MA, Tsai YH, Nagy MS, Dyal R, Wells JM, Mayhew CN, Nattiv R, Klein OD, White ES, Deutsch GH, Spence JR. Elife. 2015 Mar 24;4. doi: 10.7554/eLife.05098. PMID:25803487 DOI: http://dx.doi.org/10.7554/eLife.05098


Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Kyle W. McCracken, Emily M. Catá, Calyn M. Crawford, Katie L. Sinagoga, Michael SchumacherBriana E. Rockich, Yu-Hwai Tsai, Christopher N. Mayhew, Jason R. Spence, Yana Zavros and James M. Wells. Nature. 2014 October 29. Advanced Online Publication. 

An in vivo model of human small intestine using pluripotent stem cells. Watson CL, Mahe MM, Múnera J, Howell JC, Sundaram N, Poling HM, Schweitzer JI, Vallance JE, Mayhew CN, Sun Y, Grabowski G, Finkbeiner SR, Spence JR, Shroyer NF, Wells JM, Helmrath MA. Nature Medicine. 2014 Oct 19. PMID:25326803

Persistence and toxin production by Clostridium difficile within human intestinal organoids results in disruption of epithelial paracellular barrier function. Leslie JL**, Huang S**, Opp JS, Nagy MS, Kobayashi M, Young VB, Spence JR. Infect Immun. 2014 Oct 13. pii: IAI.02561-14. [Epub ahead of print] PMID:25312952 ** co-first authors.

 Sox17 regulates insulin secretion in the normal and pathologic mouse β cell. Jonatan D, Spence JR, Method AM, Kofron M, Sinagoga K, Haataja L, Arvan P, Deutsch GH, Wells JM. PLoS One. 2014 Aug 21;9(8):e104675. doi: 10.1371/journal.pone.0104675. eCollection 2014. PMID:25144761

De Novo Formation of Insulin-Producing "Neo-β Cell Islets" from Intestinal Crypts. Chen YJ, Finkbeiner SR, Weinblatt D, Emmett MJ, Tameire F, Yousefi M, Yang C, Maehr R, Zhou Q, Shemer R, Dor Y, Li C, Spence JR, Stanger BZ. Cell Reports. 2014, Mar 5 PMID:24613355.  

How to make an intestine.  Wells JM, Spence JR.  Development. 2014 Feb;141(4):752-60. doi: 10.1242/dev.097386.  PMID:24496613


Sox9 plays multiple roles in the lung epithelium during branching morphogenesis. Rockich BE, Hrycaj SM, Shih HP, Nagy MS, Ferguson MA, Kopp JL, Sander M, Wellik DM, Spence JR.    Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4456-64. doi: 10.1073/pnas.1311847110. Epub 2013 Nov 4.  PMID:24191021 [PubMed - in process]

Identification and Manipulation of Biliary Metaplasia in Pancreatic Tumors.  Delgiorno KE, Hall JC, Takeuchi KK, Pan FC, Halbrook CJ, Washington MK, Olive KP, Spence JR, Sipos B, Wright CV, Wells JM, Crawford HC. Gastroenterology. 2013 Aug 30. doi:pii: S0016-5085(13)01273-0. 10.1053/j.gastro.2013.08.053. [Epub ahead of print]

Induction of intestinal stem cells by R-spondin 1 and Slit2 augments chemoradioprotection.  Zhou WJ, Geng ZH, Spence JR, Geng JG. Nature. 2013 Jul 31. doi: 10.1038/nature12416. [Epub ahead of print] PMID:23903657

Endothelial PAS Domain Protein 1 Activates the Inflammatory Response in the Intestinal Epithelium to Promote Colitis in Mice. Xue X, Ramakrishnan S, Anderson E, Taylor M, Zimmermann EM, Spence JR, Huang S, Greenson JK, Shah YM.  Gastroenterology. 2013 Jul 13. doi:pii: S0016-5085(13)01010-X. 10.1053/j.gastro.2013.07.010. [Epub ahead of print]

A gutsy task: generating intestinal tissue from human pluripotent stem cells. Finkbeiner SR, Spence JR.  Dig Dis Sci. 2013 May;58(5):1176-84. doi: 10.1007/s10620-013-2620-2. Epub 2013 Mar 27. Review.


Cancer biology: a new RING to Wnt signaling. Fearon ER, Spence JR.  Curr Biol. 2012 Oct 9;22(19):R849-51. doi: 10.1016/j.cub.2012.08.002.  PMID: 23058807

2011 and earlier

Generating human intestinal tissue from pluripotent stem cells in vitro. McCracken KW, Howell JC, Wells JM, Spence JR. Nat Protoc. 2011 Nov 10;6(12):1920-8. doi: 10.1038/nprot.2011.410. PMID: 22082986 [PubMed - in process]

Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.  Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Nature. 2011 Feb 3;470(7332):105-9. Epub 2010 Dec 12.  PMID: 21151107 [PubMed - indexed for MEDLINE] Free PMC Article

Vertebrate intestinal endoderm development. Spence JR, Lauf R, Shroyer NF. Dev Dyn. 2011 Mar;240(3):501-20. doi: 10.1002/dvdy.22540. Epub 2011 Jan 18. Review. PMID: 21246663 [PubMed - indexed for MEDLINE]

Sox17 regulates organ lineage segregation of ventral foregut progenitor cells. Spence JR, Lange AW, Lin SC, Kaestner KH, Lowy AM, Kim I, Whitsett JA, Wells JM. Dev Cell. 2009 Jul;17(1):62-74.  PMID: 19619492 [PubMed - indexed for MEDLINE] Free PMC Article

Translational embryology: using embryonic principles to generate pancreatic endocrine cells from embryonic stem cells.  Spence JR, Wells JM. Dev Dyn. 2007 Dec;236(12):3218-27. Review.  PMID:17973329 [PubMed - indexed for MEDLINE] Free Article