Shangqin Guo, PhD
Associate Professor of Cell Biology
Research & Publications
Biography
News
Research Summary
We are interested in understanding the cell fate decision processes: how does a cell know what to be and what not to be? We use two primary biological model systems to investigate this question.
1. Induced pluripotency (Yamanaka reprogramming). How does a somatic cell abandon its own identity and take on pluripotency as a new identity? This process is rare but does not occur randomly. We are interested in the rare cells that undergo cell identity switching at high efficiency. We are particularly interested in a subset of hematopoietic progenitors that can undergo cell fate switching with extraordinarily high efficiency. These cells and others help us to understand the mechanism that enable high efficiency cell fate switching.
2. Maintainence of the hematopoietic stem and progenitor cell fate. Our recent work has determined that the same rare cells mentioned above, a subset of rapidly dividing hematopoietic progenitors, undergo MLL-AF9 mediated malignant transformation with high efficiency: the oncogene perpetuates this highly proliferative cell state. Therefore, the proliferative state precedes the oncogene activity and promotes transformation. We are actively working on elucidating the mechanisms that maintain or perpetuate the hematopoietic progenitor cell fate.
Overall, our long term goal is to deduce the rules of cell fate control to help create desired cell types for cell replacement therapies and to eliminate the emergence of harmful cell types such as cancer.
Specialized Terms: Cell fate control; Reprogramming; Hematopoietic stem and progenitors; Leukemogenesis; Cell cycle; live-cell imaging
Coauthors
Research Interests
Cell Biology; Hematopoietic Stem Cells; Leukemia, Experimental; Cellular Reprogramming
Research Image
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Growing colonies during Yamanaka reprogramming captured by live-cell imaging. Green color indicates pluripotency (Oct4:GFP). Red color indicates G1 cell cycle phase (FUCCI).
Selected Publications
- Serum Response Factor Reduces Gene Expression Noise and Confers Cell State StabilityZhang J, Wu Q, Hu X, Wang Y, Lu J, Chakraborty R, Martin K, Guo S. Serum Response Factor Reduces Gene Expression Noise and Confers Cell State Stability. Stem Cells 2023, 41: 907-915. PMID: 37386941, DOI: 10.1093/stmcls/sxad051.
- Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signalingFeng X, Sun R, Lee M, Chen X, Guo S, Geng H, Müschen M, Choi J, Pereira J. Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling. ELife 2023, 12: e83533. PMID: 36912771, PMCID: PMC10042536, DOI: 10.7554/elife.83533.
- Incorporating signaling dynamics into fate decisionGuo S. Incorporating signaling dynamics into fate decision. Blood 2022, 140: 79-80. PMID: 35834282, PMCID: PMC9283969, DOI: 10.1182/blood.2022016420.
- Integrating mechanical signals into cellular identityCarley E, King MC, Guo S. Integrating mechanical signals into cellular identity. Trends In Cell Biology 2022, 32: 669-680. PMID: 35337714, PMCID: PMC9288541, DOI: 10.1016/j.tcb.2022.02.006.
- EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesisHidalgo D, Bejder J, Pop R, Gellatly K, Hwang Y, Maxwell Scalf S, Eastman AE, Chen JJ, Zhu LJ, Heuberger JAAC, Guo S, Koury MJ, Nordsborg NB, Socolovsky M. EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis. Nature Communications 2021, 12: 7334. PMID: 34921133, PMCID: PMC8683474, DOI: 10.1038/s41467-021-27562-4.
- Epor Stimulates Rapid Cycling and Larger Red Cells during Mouse and Human ErythropoiesisHidalgo D, Bejder J, Pop R, Gellatly K, Hwang Y, Scalf S, Eastman A, Chen J, Zhu L, Heuberger J, Guo S, Koury M, Nordsborg N, Socolovsky M. Epor Stimulates Rapid Cycling and Larger Red Cells during Mouse and Human Erythropoiesis. Blood 2021, 138: 852. DOI: 10.1182/blood-2021-154403.
- Novel Fluorescent Timer Tool Enables Characterization of Erythropoietic Differentiation Based on Differential Cell Cycling SpeedsModepalli S, Eastman A, Shaw C, Guo S, Hattangadi S, Kupfer G. Novel Fluorescent Timer Tool Enables Characterization of Erythropoietic Differentiation Based on Differential Cell Cycling Speeds. Blood 2020, 136: 27-28. DOI: 10.1182/blood-2020-141666.
- Reprogramming progressive cells display low CAG promoter activityHu X, Wu Q, Zhang J, Kim J, Chen X, Hartman AA, Eastman AE, Park I, Guo S. Reprogramming progressive cells display low CAG promoter activity. Stem Cells 2020, 39: 43-54. PMID: 33075202, PMCID: PMC7821215, DOI: 10.1002/stem.3295.
- 2014 – FLUORESCENT CELL CYCLE TIMER ENABLED ANALYSIS OF NORMAL AND INEFFECTIVE ERYTHROPOIESISModepalli S, Eastman A, Shaw C, Guo S, Hattangadi S, Kupfer G. 2014 – FLUORESCENT CELL CYCLE TIMER ENABLED ANALYSIS OF NORMAL AND INEFFECTIVE ERYTHROPOIESIS. Experimental Hematology 2020, 88: s32. DOI: 10.1016/j.exphem.2020.09.176.
- The palette of techniques for cell cycle analysisEastman AE, Guo S. The palette of techniques for cell cycle analysis. FEBS Letters 2020, 594: 2084-2098. PMID: 32441778, PMCID: PMC9261528, DOI: 10.1002/1873-3468.13842.
- Resolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent ReporterEastman AE, Chen X, Hu X, Hartman AA, Morales A, Yang C, Lu J, Kueh HY, Guo S. Resolving Cell Cycle Speed in One Snapshot with a Live-Cell Fluorescent Reporter. Cell Reports 2020, 31: 107804. PMID: 32579930, PMCID: PMC7418154, DOI: 10.1016/j.celrep.2020.107804.
- YAP Non-cell-autonomously Promotes Pluripotency Induction in Mouse CellsHartman AA, Scalf SM, Zhang J, Hu X, Chen X, Eastman AE, Yang C, Guo S. YAP Non-cell-autonomously Promotes Pluripotency Induction in Mouse Cells. Stem Cell Reports 2020, 14: 730-743. PMID: 32243844, PMCID: PMC7160372, DOI: 10.1016/j.stemcr.2020.03.006.
- High-speed automatic characterization of rare events in flow cytometric dataQi Y, Fang Y, Sinclair DR, Guo S, Alberich-Jorda M, Lu J, Tenen DG, Kharas MG, Pyne S. High-speed automatic characterization of rare events in flow cytometric data. PLOS ONE 2020, 15: e0228651. PMID: 32045462, PMCID: PMC7012421, DOI: 10.1371/journal.pone.0228651.
- Publisher Correction: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitorsChen X, Burkhardt DB, Hartman AA, Hu X, Eastman AE, Sun C, Wang X, Zhong M, Krishnaswamy S, Guo S. Publisher Correction: MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors. Nature Communications 2020, 11: 681. PMID: 31996673, PMCID: PMC6989496, DOI: 10.1038/s41467-020-14428-4.
- MLL-AF9 initiates transformation from fast-proliferating myeloid progenitorsChen X, Burkhardt DB, Hartman AA, Hu X, Eastman AE, Sun C, Wang X, Zhong M, Krishnaswamy S, Guo S. MLL-AF9 initiates transformation from fast-proliferating myeloid progenitors. Nature Communications 2019, 10: 5767. PMID: 31852898, PMCID: PMC6920141, DOI: 10.1038/s41467-019-13666-5.
- Cell cycle dynamics in the reprogramming of cellular identityHu X, Eastman AE, Guo S. Cell cycle dynamics in the reprogramming of cellular identity. FEBS Letters 2019, 593: 2840-2852. PMID: 31562821, DOI: 10.1002/1873-3468.13625.
- Collisions on the Busy DNA Highway Set Up Barriers for ReprogrammingHu X, Guo S. Collisions on the Busy DNA Highway Set Up Barriers for Reprogramming. Cell Stem Cell 2019, 25: 451-453. PMID: 31585090, DOI: 10.1016/j.stem.2019.09.007.
- Targeting Fibrotic Signaling: A Review of Current Literature and Identification of Future Therapeutic Targets to Improve Wound Healing.Hetzler PT, Dash BC, Guo S, Hsia HC. Targeting Fibrotic Signaling: A Review of Current Literature and Identification of Future Therapeutic Targets to Improve Wound Healing. Annals Of Plastic Surgery 2019, 83: e92-e95. PMID: 31246672, PMCID: PMC6851445, DOI: 10.1097/sap.0000000000001955.
- MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activationHu X, Liu ZZ, Chen X, Schulz VP, Kumar A, Hartman AA, Weinstein J, Johnston JF, Rodriguez EC, Eastman AE, Cheng J, Min L, Zhong M, Carroll C, Gallagher PG, Lu J, Schwartz M, King MC, Krause DS, Guo S. MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation. Nature Communications 2019, 10: 1695. PMID: 30979898, PMCID: PMC6461646, DOI: 10.1038/s41467-019-09636-6.
- Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to PluripotencyHernandez C, Wang Z, Ramazanov B, Tang Y, Mehta S, Dambrot C, Lee YW, Tessema K, Kumar I, Astudillo M, Neubert TA, Guo S, Ivanova NB. Dppa2/4 Facilitate Epigenetic Remodeling during Reprogramming to Pluripotency. Cell Stem Cell 2018, 23: 396-411.e8. PMID: 30146411, PMCID: PMC6128737, DOI: 10.1016/j.stem.2018.08.001.
- miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanismLiu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, Kyba M, Fan R, Guo S, Lu J. miR-125b promotes MLL-AF9–driven murine acute myeloid leukemia involving a VEGFA-mediated non–cell-intrinsic mechanism. Blood 2017, 129: 1491-1502. PMID: 28053194, PMCID: PMC5356452, DOI: 10.1182/blood-2016-06-721027.
- A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regionsCheng J, Roden CA, Pan W, Zhu S, Baccei A, Pan X, Jiang T, Kluger Y, Weissman SM, Guo S, Flavell RA, Ding Y, Lu J. A Molecular Chipper technology for CRISPR sgRNA library generation and functional mapping of noncoding regions. Nature Communications 2016, 7: 11178. PMID: 27025950, PMCID: PMC4820989, DOI: 10.1038/ncomms11178.
- Choosing Cell Fate Through a Dynamic Cell CycleChen X, Hartman A, Guo S. Choosing Cell Fate Through a Dynamic Cell Cycle. Current Stem Cell Reports 2015, 1: 129-138. PMID: 28725536, PMCID: PMC5487535, DOI: 10.1007/s40778-015-0018-0.
- Nonstochastic Reprogramming from a Privileged Somatic Cell StateGuo S, Zi X, Schulz VP, Cheng J, Zhong M, Koochaki SH, Megyola CM, Pan X, Heydari K, Weissman SM, Gallagher PG, Krause DS, Fan R, Lu J. Nonstochastic Reprogramming from a Privileged Somatic Cell State. Cell 2014, 156: 649-662. PMID: 24486105, PMCID: PMC4318260, DOI: 10.1016/j.cell.2014.01.020.
- An Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant HematopoiesisCheng J, Guo S, Chen S, Mastriano SJ, Liu C, D’Alessio A, Hysolli E, Guo Y, Yao H, Megyola CM, Li D, Liu J, Pan W, Roden CA, Zhou XL, Heydari K, Chen J, Park IH, Ding Y, Zhang Y, Lu J. An Extensive Network of TET2-Targeting MicroRNAs Regulates Malignant Hematopoiesis. Cell Reports 2013, 5: 471-481. PMID: 24120864, PMCID: PMC3834864, DOI: 10.1016/j.celrep.2013.08.050.
- Piwi Genes Are Dispensable for Normal Hematopoiesis in MiceNolde MJ, Cheng EC, Guo S, Lin H. Piwi Genes Are Dispensable for Normal Hematopoiesis in Mice. PLOS ONE 2013, 8: e71950. PMID: 24058407, PMCID: PMC3751959, DOI: 10.1371/journal.pone.0071950.
- Dynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse ImagingMegyola CM, Gao Y, Teixeira AM, Cheng J, Heydari K, Cheng E, Nottoli T, Krause DS, Lu J, Guo S. Dynamic Migration and Cell‐Cell Interactions of Early Reprogramming Revealed by High‐Resolution Time‐Lapse Imaging. Stem Cells 2013, 31: 895-905. PMID: 23335078, PMCID: PMC4309553, DOI: 10.1002/stem.1323.
- An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury ResponseAdams BD, Guo S, Bai H, Guo Y, Megyola CM, Cheng J, Heydari K, Xiao C, Reddy EP, Lu J. An In Vivo Functional Screen Uncovers miR-150-Mediated Regulation of Hematopoietic Injury Response. Cell Reports 2012, 2: 1048-1060. PMID: 23084747, PMCID: PMC3487471, DOI: 10.1016/j.celrep.2012.09.014.
- Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasmsGuo S, Bai H, Megyola CM, Halene S, Krause DS, Scadden DT, Lu J. Complex oncogene dependence in microRNA-125a–induced myeloproliferative neoplasms. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16636-16641. PMID: 23012470, PMCID: PMC3478612, DOI: 10.1073/pnas.1213196109.
- An In Vivo Functional Screen Identifies miRNA-150 As a Regulator of Hematopoietic Regeneration Post Chemotherapeutic InjuryAdams B, Guo S, Bai H, Xiao C, Reddy E, Lu J. An In Vivo Functional Screen Identifies miRNA-150 As a Regulator of Hematopoietic Regeneration Post Chemotherapeutic Injury. Blood 2011, 118: 2333. DOI: 10.1182/blood.v118.21.2333.2333.
- A microRNA regulating adult hematopoietic stem cellsGuo S, Scadden DT. A microRNA regulating adult hematopoietic stem cells. Cell Cycle 2010, 9: 3637-3638. PMID: 20855952, DOI: 10.4161/cc.9.18.13174.
- MicroRNA miR-125a controls hematopoietic stem cell numberGuo S, Lu J, Schlanger R, Zhang H, Wang JY, Fox MC, Purton LE, Fleming HH, Cobb B, Merkenschlager M, Golub TR, Scadden DT. MicroRNA miR-125a controls hematopoietic stem cell number. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 14229-14234. PMID: 20616003, PMCID: PMC2922532, DOI: 10.1073/pnas.0913574107.
- Compartmentalized organization: a common and required feature of stem cell niches?Greco V, Guo S. Compartmentalized organization: a common and required feature of stem cell niches? Development 2010, 137: 1586-1594. PMID: 20430743, PMCID: PMC2860245, DOI: 10.1242/dev.041103.
- Bone progenitor dysfunction induces myelodysplasia and secondary leukaemiaRaaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature 2010, 464: 852-857. PMID: 20305640, PMCID: PMC3422863, DOI: 10.1038/nature08851.
- Niche Induced Myelodysplasia and Secondary Hematopoietic Neoplasia Caused by Deletion of Dicer1 in Osteoprogenitor Cells.Raaijmakers M, Mukherjee S, Guo S, Kobayashi T, Schoonmaker J, Aung Z, Ebert B, Al-Shahrour F, Hasserjian R, Vallet S, Scadden E, Lin C, Scadden D. Niche Induced Myelodysplasia and Secondary Hematopoietic Neoplasia Caused by Deletion of Dicer1 in Osteoprogenitor Cells. Blood 2009, 114: 247. DOI: 10.1182/blood.v114.22.247.247.
- MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte ProgenitorsLu J, Guo S, Ebert BL, Zhang H, Peng X, Bosco J, Pretz J, Schlanger R, Wang JY, Mak RH, Dombkowski DM, Preffer FI, Scadden DT, Golub TR. MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors. Developmental Cell 2008, 14: 843-853. PMID: 18539114, PMCID: PMC2688789, DOI: 10.1016/j.devcel.2008.03.012.
- Green tea polyphenols reverse cooperation between c-Rel and CK2 that induces the aryl hydrocarbon receptor, slug, and an invasive phenotype.Belguise K, Guo S, Yang S, Rogers AE, Seldin DC, Sherr DH, Sonenshein GE. Green tea polyphenols reverse cooperation between c-Rel and CK2 that induces the aryl hydrocarbon receptor, slug, and an invasive phenotype. Cancer Research 2007, 67: 11742-50. PMID: 18089804, DOI: 10.1158/0008-5472.CAN-07-2730.
- Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells.Belguise K, Guo S, Sonenshein GE. Activation of FOXO3a by the green tea polyphenol epigallocatechin-3-gallate induces estrogen receptor alpha expression reversing invasive phenotype of breast cancer cells. Cancer Research 2007, 67: 5763-70. PMID: 17575143, DOI: 10.1158/0008-5472.CAN-06-4327.
- Microarray-Assisted Pathway Analysis Identifies Mitogen-Activated Protein Kinase Signaling as a Mediator of Resistance to the Green Tea Polyphenol Epigallocatechin 3-Gallate in Her-2/neu–Overexpressing Breast Cancer CellsGuo S, Lu J, Subramanian A, Sonenshein GE. Microarray-Assisted Pathway Analysis Identifies Mitogen-Activated Protein Kinase Signaling as a Mediator of Resistance to the Green Tea Polyphenol Epigallocatechin 3-Gallate in Her-2/neu–Overexpressing Breast Cancer Cells. Cancer Research 2006, 66: 5322-5329. PMID: 16707458, DOI: 10.1158/0008-5472.can-05-4287.
- Inducible IkappaB kinase/IkappaB kinase epsilon expression is induced by CK2 and promotes aberrant nuclear factor-kappaB activation in breast cancer cells.Eddy SF, Guo S, Demicco EG, Romieu-Mourez R, Landesman-Bollag E, Seldin DC, Sonenshein GE. Inducible IkappaB kinase/IkappaB kinase epsilon expression is induced by CK2 and promotes aberrant nuclear factor-kappaB activation in breast cancer cells. Cancer Research 2005, 65: 11375-83. PMID: 16357145, DOI: 10.1158/0008-5472.CAN-05-1602.
- Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenz[a]anthracene.Guo S, Yang S, Taylor C, Sonenshein GE. Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenz[a]anthracene. The Journal Of Nutrition 2005, 135: 2978S-2986S. PMID: 16317158, DOI: 10.1093/jn/135.12.2978S.
- Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway.Guo S, Sonenshein GE. Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Molecular And Cellular Biology 2004, 24: 8681-90. PMID: 15367686, PMCID: PMC516736, DOI: 10.1128/MCB.24.19.8681-8690.2004.
- Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells.Pianetti S, Guo S, Kavanagh KT, Sonenshein GE. Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells. Cancer Research 2002, 62: 652-5. PMID: 11830514.