Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells

被引：20

作者：

Allison, Thomas F. ^{[1
]}

Smith, Andrew J. H. ^{[3
,5
]}

Anastassiadis, Konstantinos ^{[4
]}

Sloane-Stanley, Jackie ^{[5
]}

Biga, Veronica ^{[2
,7
]}

Stavish, Dylan ^{[1
]}

Hackland, James ^{[1
]}

Sabri, Shan ^{[6
]}

Langerman, Justin ^{[6
]}

Jones, Mark ^{[1
]}

Plath, Kathrin ^{[6
]}

Coca, Daniel ^{[2
]}

Barbaric, Ivana ^{[1
]}

Gokhale, Paul ^{[1
]}

Andrews, Peter W. ^{[1
]}

机构：

[1] Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England

[2] Univ Sheffield, Dept Automat Control & Syst Engn, Signal Proc & Complex Syst Grp, Sheffield S10 2TN, S Yorkshire, England

[3] Univ Edinburgh, Inst Stem Cell Res, Sch Biol Sci, MRC Ctr Regenerat Med, Edinburgh EH16 4UU, Midlothian, Scotland

[4] Tech Univ Dresden, Biotechnol Ctr, Stem Cell Engn, D-01307 Dresden, Germany

[5] Univ Oxford, MRC Weatherall Inst Mol Med, John Radcliffe Hosp, Radcliffe Dept Med,MRC Mol Haematol Unit, Oxford OX3 9DS, England

[6] Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90024 USA

[7] Univ Manchester, Sch Med, Fac Biol & Hlth, Manchester M13 9PT, Lancs, England

来源：

STEM CELL REPORTS | 2018年 / 10卷 / 06期

基金：

英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

LINEAGE COMMITMENT; PRIMITIVE ENDODERM; HUMAN FIBROBLASTS; SURFACE-ANTIGENS; GLOBO-SERIES; DIFFERENTIATION; CULTURE; STATES; EQUILIBRIUM; POPULATIONS;

D O I：

10.1016/j.stemcr.2018.04.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete sub-states within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single-cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm-biased stem cell state.

引用

页码：1895 / 1907

页数：13

共 36 条

[1] Role of SOX2 in maintaining pluripotency of human embryonic stem cells [J].

Adachi, Keiko ;

Suemori, Hirofumi ;

Yasuda, Shin-ya ;

Nakatsuji, Norio ;

Kawase, Eihachiro .

GENES TO CELLS, 2010, 15 (05) :455-469

[2] Characterization of human embryonic stem cell lines by the International Stem Cell Initiative [J].

Adewumi, Oluseun ;

Aflatoonian, Behrouz ;

Ahrlund-Richter, Lars ;

Amit, Michal ;

Andrews, Peter W. ;

Beighton, Gemma ;

Bello, Paul A. ;

Benvenisty, Nissim ;

Berry, Lorraine S. ;

Bevan, Simon ;

Blum, Barak ;

Brooking, Justin ;

Chen, Kevin G. ;

Choo, Andre B. H. ;

Churchill, Gary A. ;

Corbel, Marie ;

Damjanov, Ivan ;

Draper, Jon S. ;

Dvorak, Petr ;

Emanuelsson, Katarina ;

Fleck, Roland A. ;

Ford, Angela ;

Gertow, Karin ;

Gertsenstein, Marina ;

Gokhale, Paul J. ;

Hamilton, Rebecca S. ;

Hampl, Ales ;

Healy, Lyn E. ;

Hovatta, Outi ;

Hyllner, Johan ;

Imreh, Marta P. ;

Itskovitz-Eldor, Joseph ;

Jackson, Jamie ;

Johnson, Jacqueline L. ;

Jones, Mark ;

Kee, Kehkooi ;

King, Benjamin L. ;

Knowles, Barbara B. ;

Lako, Majlinda ;

Lebrin, Franck ;

Mallon, Barbara S. ;

Manning, Daisy ;

Mayshar, Yoav ;

Mckay, Ronald D. G. ;

Michalska, Anna E. ;

Mikkola, Milla ;

Mileikovsky, Masha ;

Minger, Stephen L. ;

Moore, Harry D. ;

Mummery, Christine L. .

NATURE BIOTECHNOLOGY, 2007, 25 (07) :803-816

[3] Generation of Sheffield (Shef) human embryonic stem cell lines using a microdrop culture system [J].

Aflatoonian, Behrouz ;

Ruban, Ludmila ;

Shamsuddin, Shamsul ;

Baker, Duncan ;

Andrews, Peter ;

Moore, Harry .

IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 2010, 46 (3-4) :236-241

[4] CELL-SURFACE ANTIGENS OF A CLONAL HUMAN EMBRYONAL CARCINOMA CELL-LINE - MORPHOLOGICAL AND ANTIGENIC DIFFERENTIATION IN CULTURE [J].

ANDREWS, PW ;

GOODFELLOW, PN ;

SHEVINSKY, LH ;

BRONSON, DL ;

KNOWLES, BB .

INTERNATIONAL JOURNAL OF CANCER, 1982, 29 (05) :523-531

[5] Gene expression heterogeneities in embryonic stem cell populations: origin and function [J].

Ariasi, Alfonso Martinez ;

Brickman, Joshua M. .

CURRENT OPINION IN CELL BIOLOGY, 2011, 23 (06) :650-656

[6] Time-Lapse Analysis of Human Embryonic Stem Cells Reveals Multiple Bottlenecks Restricting Colony Formation and Their Relief upon Culture Adaptation [J].

Barbaric, Ivana ;

Biga, Veronica ;

Gokhale, Paul J. ;

Jones, Mark ;

Stavish, Dylan ;

Glen, Adam ;

Coca, Daniel ;

Andrews, Peter W. .

STEM CELL REPORTS, 2014, 3 (01) :142-155

[7] Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors [J].

Blauwkamp, Timothy A. ;

Nigam, Shelly ;

Ardehali, Reza ;

Weissman, Irving L. ;

Nusse, Roel .

NATURE COMMUNICATIONS, 2012, 3

[8] Oct-4: The almighty POUripotent regulator? [J].

Buitrago, William ;

Roop, Dennis R. .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2007, 127 (02) :260-262

[9] Functional Heterogeneity of Embryonic Stem Cells Revealed through Translational Amplification of an Early Endodermal Transcript [J].

Canham, Maurice A. ;

Sharov, Alexei A. ;

Ko, Minoru S. H. ;

Brickman, Joshua M. .

PLOS BIOLOGY, 2010, 8 (05)

[10] Nanog safeguards pluripotency and mediates germline development [J].

Chambers, Ian ;

Silva, Jose ;

Colby, Douglas ;

Nichols, Jennifer ;

Nijmeijer, Bianca ;

Robertson, Morag ;

Vrana, Jan ;

Jones, Ken ;

Grotewold, Lars ;

Smith, Austin .

NATURE, 2007, 450 (7173) :1230-U8

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