Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved..
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates. The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells. Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive and primed cells. Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Cell reports - 21(2017), 10 vom: 05. Dez., Seite 2965-2977 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chandrasekaran, Sriram [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Cell fate |
|---|
| Anmerkungen: |
Date Completed 17.07.2018 Date Revised 10.04.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.celrep.2017.07.048 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM278772129 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM278772129 | ||
| 003 | DE-627 | ||
| 005 | 20231226194555.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.celrep.2017.07.048 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0929.xml |
| 035 | |a (DE-627)NLM278772129 | ||
| 035 | |a (NLM)29212039 | ||
| 035 | |a (PII)S2211-1247(17)31027-6 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chandrasekaran, Sriram |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Comprehensive Mapping of Pluripotent Stem Cell Metabolism Using Dynamic Genome-Scale Network Modeling |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.07.2018 | ||
| 500 | |a Date Revised 10.04.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates. The model also predicts that the pluripotency factor Lin28 regulates this one-carbon metabolic pathway, which we validate using metabolomics data from Lin28-deficient cells. Moreover, we identify and validate metabolic reactions related to S-adenosyl-methionine production that can differentially impact histone methylation in naive and primed cells. Our network-based approach provides a framework for characterizing metabolic changes influencing pluripotency and cell fate | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cell fate | |
| 650 | 4 | |a genome-scale modeling | |
| 650 | 4 | |a histone methylation | |
| 650 | 4 | |a metabolic network | |
| 650 | 4 | |a metabolism | |
| 650 | 4 | |a naive (ground) state | |
| 650 | 4 | |a pluripotency | |
| 650 | 4 | |a primed state | |
| 650 | 4 | |a stem cell biology | |
| 650 | 4 | |a systems biology | |
| 650 | 7 | |a Histones |2 NLM | |
| 700 | 1 | |a Zhang, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Ross, Christian A |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yu-Chung |e verfasserin |4 aut | |
| 700 | 1 | |a Asara, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Daley, George Q |e verfasserin |4 aut | |
| 700 | 1 | |a Collins, James J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell reports |d 2012 |g 21(2017), 10 vom: 05. Dez., Seite 2965-2977 |w (DE-627)NLM217067492 |x 2211-1247 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2017 |g number:10 |g day:05 |g month:12 |g pages:2965-2977 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.celrep.2017.07.048 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2017 |e 10 |b 05 |c 12 |h 2965-2977 | ||