Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution

被引：813

作者：

Corces, M. Ryan ^{[1
,2
,3
]}

Buenrostro, Jason D. ^{[3
,4
,5
]}

Wu, Beijing ^{[4
]}

Greenside, Peyton G. ^{[4
,6
]}

Chan, Steven M. ^{[7
]}

Koenig, Julie L. ^{[1
,2
]}

Snyder, Michael P. ^{[3
,4
]}

Pritchard, Jonathan K. ^{[4
,8
,9
]}

Kundaje, Anshul ^{[4
,10
]}

Gkeenleaf, William J. ^{[3
,4
]}

Majeti, Ravindra ^{[1
,2
]}

Chang, Howard Y. ^{[3
]}

机构：

[1] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[5] Harvard Univ, Broad Inst MIT & Harvard, Cambridge, MA 02138 USA

[6] Stanford Univ, Sch Med, Program Biomed Informat, Stanford, CA 94305 USA

[7] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[8] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[9] Howard Hughes Med Inst, Chevy Chase, MD USA

[10] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

来源：

NATURE GENETICS | 2016年 / 48卷 / 10期

基金：

美国国家科学基金会;

关键词：

ACUTE MYELOID-LEUKEMIA; EPIGENETIC REGULATORS; TRANSCRIPTION FACTORS; CLONAL HEMATOPOIESIS; DNA-BINDING; STEM-CELLS; EXPRESSION; MICE; IDENTIFICATION; COMMITMENT;

D O I：

10.1038/ng.3646

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

We define the chromatin accessibility and transcriptional landscapes in 13 human primary blood cell types that span the hematopoietic hierarchy. Exploiting the finding that the enhancer landscape better reflects cell identity than mRNA levels, we enable 'enhancer cytometry' for enumeration of pure cell types from complex populations. We identify regulators governing hematopoietic differentiation and further show the lineage ontogeny of genetic elements linked to diverse human diseases. In acute myeloid leukemia (AML), chromatin accessibility uncovers unique regulatory evolution in cancer cells with a progressively increasing mutation burden. Single AML cells exhibit distinctive mixed regulome profiles corresponding to disparate developmental stages. A method to account for this regulatory heterogeneity identified cancer-specific deviations and implicated HOX factors as key regulators of preleukemic hematopoietic stem cell characteristics. Thus, regulome dynamics can provide diverse insights into hematopoietic development and disease.

引用

页码：1193 / 1203

页数：11

共 45 条

[1]

PROPOSALS FOR CLASSIFICATION OF ACUTE LEUKEMIAS [J].

BENNETT, JM ;

CATOVSKY, D ;

DANIEL, MT ;

FLANDRIN, G ;

GALTON, DAG ;

GRALNICK, HR ;

SULTAN, C .

BRITISH JOURNAL OF HAEMATOLOGY, 1976, 33 (04) :451-&

[2]

Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell [J].

Bonnet, D ;

Dick, JE .

NATURE MEDICINE, 1997, 3 (07) :730-737

[3]

Single-cell chromatin accessibility reveals principles of regulatory variation [J].

Buenostro, Jason D. ;

Wu, Beijing ;

Litzenburger, Ulrike M. ;

Ruff, Dave ;

Gonzales, Michael L. ;

Snyder, Michael P. ;

Chang, Howard Y. ;

Greenleaf, William J. .

NATURE, 2015, 523 (7561) :486-U264

[4]

Buenrostro JD, 2013, NAT METHODS, V10, P1213, DOI [10.1038/nmeth.2688, 10.1038/NMETH.2688]

[5]

Hematopoietic stem cell fate is established by the Notch-Runx pathway [J].

Burns, CE ;

Traver, D ;

Mayhall, E ;

Shepard, JL ;

Zon, LI .

GENES & DEVELOPMENT, 2005, 19 (19) :2331-2342

[6]

Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific Chromatin Signature [J].

Cauchy, Pierre ;

James, Sally R. ;

Zacarias-Cabeza, Joaquin ;

Ptasinska, Anetta ;

Imperato, Maria Rosaria ;

Assi, Salam A. ;

Piper, Jason ;

Canestraro, Martina ;

Hoogenkamp, Maarten ;

Raghavan, Manoj ;

Loke, Justin ;

Akiki, Susanna ;

Clokie, Samuel J. ;

Richards, Stephen J. ;

Westhead, David R. ;

Griffiths, Michael J. ;

Ott, Sascha ;

Bonifer, Constanze ;

Cockerill, Peter N. .

CELL REPORTS, 2015, 12 (05) :821-836

[7]

Transcriptional diversity during lineage commitment of human blood progenitors [J].

Chen, Lu ;

Kostadima, Myrto ;

Martens, Joost H. A. ;

Canu, Giovanni ;

Garcia, Sara P. ;

Turro, Ernest ;

Downes, Kate ;

Macaulay, Iain C. ;

Bielczyk-Maczynska, Ewa ;

Coe, Sophia ;

Farrow, Samantha ;

Poudel, Pawan ;

Burden, Frances ;

Jansen, Sjoert B. G. ;

Astle, William J. ;

Attwood, Antony ;

Bariana, Tadbir ;

de Bono, Bernard ;

Breschi, Alessandra ;

Chambers, John C. ;

Choudry, Fizzah A. ;

Clarke, Laura ;

Coupland, Paul ;

van der Ent, Martijn ;

Erber, Wendy N. ;

Jansen, Joop H. ;

Favier, Remi ;

Fenech, Matthew E. ;

Foad, Nicola ;

Freson, Kathleen ;

van Geet, Chris ;

Gomez, Keith ;

Guigo, Roderic ;

Hampshire, Daniel ;

Kelly, Anne M. ;

Kerstens, Hindrik H. D. ;

Kooner, Jaspal S. ;

Laffan, Michael ;

Lentaigne, Claire ;

Labalette, Charlotte ;

Martin, Tiphaine ;

Meacham, Stuart ;

Mumford, Andrew ;

Nuernberg, Sylvia ;

Palumbo, Emilio ;

van der Reijden, Bert A. ;

Richardson, David ;

Sammut, Stephen J. ;

Slodkowicz, Greg ;

Tamuri, Asif U. .

SCIENCE, 2014, 345 (6204) :1580-+

[8]

Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission [J].

Corces-Zimmerman, M. Ryan ;

Hong, Wan-Jen ;

Weissman, Irving L. ;

Medeiros, Bruno C. ;

Majeti, Ravindra .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (07) :2548-2553

[9]

Acute Myeloid Leukemia [J].

Doehner, Hartmut ;

Weisdorf, Daniel J. ;

Bloomfield, Clara D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (12) :1136-1152

[10]

Genetic and epigenetic fine mapping of causal autoimmune disease variants [J].

Farh, Kyle Kai-How ;

Marson, Alexander ;

Zhu, Jiang ;

Kleinewietfeld, Markus ;

Housley, William J. ;

Beik, Samantha ;

Shoresh, Noam ;

Whitton, Holly ;

Ryan, Russell J. H. ;

Shishkin, Alexander A. ;

Hatan, Meital ;

Carrasco-Alfonso, Marlene J. ;

Mayer, Dita ;

Luckey, C. John ;

Patsopoulos, Nikolaos A. ;

De Jager, Philip L. ;

Kuchroo, Vijay K. ;

Epstein, Charles B. ;

Daly, Mark J. ;

Hafler, David A. ;

Bernstein, Bradley E. .

NATURE, 2015, 518 (7539) :337-343

← 1 2 3 4 5 →