دورية أكاديمية
Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress.
| العنوان: | Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress. |
|---|---|
| المؤلفون: | Do BT; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Health Sciences and Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Hsu PP; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02113, USA; Rogel Cancer Center and Division of Hematology and Oncology, Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: hsupe@med.umich.edu., Vermeulen SY; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Wang Z; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Hirz T; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02113, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA., Abbott KL; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Aziz N; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02113, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA., Replogle JM; Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA 94158, USA., Bjelosevic S; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Paolino J; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Nelson SA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Block S; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Darnell AM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Ferreira R; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA., Zhang H; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02113, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA., Milosevic J; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02113, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA., Schmidt DR; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Chidley C; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA., Harris IS; Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA., Weissman JS; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA., Pikman Y; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Stegmaier K; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Cheloufi S; Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA; Stem Cell Center, University of California, Riverside, Riverside, CA 92521, USA; Center for RNA Biology and Medicine, Riverside, CA 92521, USA., Su XA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Sykes DB; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02113, USA; Harvard Stem Cell Institute, Cambridge, MA 02139, USA., Vander Heiden MG; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mvh@mit.edu. |
| المصدر: | Developmental cell [Dev Cell] 2024 May 30. Date of Electronic Publication: 2024 May 30. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101120028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1551 (Electronic) Linking ISSN: 15345807 NLM ISO Abbreviation: Dev Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2001- |
| مستخلص: | Control of cellular identity requires coordination of developmental programs with environmental factors such as nutrient availability, suggesting that perturbing metabolism can alter cell state. Here, we find that nucleotide depletion and DNA replication stress drive differentiation in human and murine normal and transformed hematopoietic systems, including patient-derived acute myeloid leukemia (AML) xenografts. These cell state transitions begin during S phase and are independent of ATR/ATM checkpoint signaling, double-stranded DNA break formation, and changes in cell cycle length. In systems where differentiation is blocked by oncogenic transcription factor expression, replication stress activates primed regulatory loci and induces lineage-appropriate maturation genes despite the persistence of progenitor programs. Altering the baseline cell state by manipulating transcription factor expression causes replication stress to induce genes specific for alternative lineages. The ability of replication stress to selectively activate primed maturation programs across different contexts suggests a general mechanism by which changes in metabolism can promote lineage-appropriate cell state transitions. Competing Interests: Declaration of interests D.B.S. is a co-founder of and holds equity in Clear Creek Bio. M.G.V.H. is on the scientific advisory board of Agios Pharmaceuticals, iTeos Therapeutics, Drioa Ventures, Sage Therapeutics, Lime Therapeutics, Pretzel Therapeutics, and Auron Therapeutics, and is on the advisory board of Developmental Cell. P.P.H. has consulted for Auron Therapeutics. J.S.W. serves as an advisor to and/or has equity in KSQ Therapeutics, Maze Therapeutics, and 5AM Ventures. J.M.R. consults for Maze Therapeutics, Waypoint Bio, and Third Rock Ventures. I.S.H. reports financial support from Kojin Therapeutics and consulting fees for Ono Pharma USA. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | P30 CA014051 United States CA NCI NIH HHS; R35 CA242379 United States CA NCI NIH HHS; R35 GM151004 United States GM NIGMS NIH HHS; U54 DK106829 United States DK NIDDK NIH HHS |
| فهرسة مساهمة: | Keywords: cancer; cell fate; cell state; dependencies; differentiation; epigenetics; hematopoiesis; metabolism; nucleotides; replication; replication stress |
| تواريخ الأحداث: | Date Created: 20240601 Latest Revision: 20240624 |
| رمز التحديث: | 20240624 |
| DOI: | 10.1016/j.devcel.2024.05.010 |
| PMID: | 38823395 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-1551 |
|---|---|
| DOI: | 10.1016/j.devcel.2024.05.010 |