Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Theoretical and Natural Science
Vol. 35, 26 April 2024
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The stochasticity in organismal development: Stem cell heterogeneity
* Author to whom correspondence should be addressed.
Abstract
Organismal development was traditionally believed to be a tightly regulated process; however, recent discoveries have uncovered its underlying stochasticity. Numerous questions remain unsolved regarding the effect of stochasticity, the origin of variability, to what extent stochasticity influences development, and how the balance between randomness and robustness is maintained. This dissertation provides an overview of beneficial and detrimental aspects of stochastic events in the organismal development process, with a particular focus on explaining how intrinsic and extrinsic noise contribute to stem cell heterogeneity, which plays a crucial role in their differentiation and self-renewal. Furthermore, the current research limitations and significance of future exploration in this field were highlighted in the end.
Keywords
organismal development, stochasticity, stem cell heterogeneity, intrinsic and extrinsic noise
References
1. J. M. Hataye et al., ‘Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread’, Cell Host & Microbe, vol. 26, no. 6, pp. 748-763.e20, Dec. 2019, doi: 10.1016/j.chom.2019.10.006.
2. L. S. Weinberger, J. C. Burnett, J. E. Toettcher, A. P. Arkin, and D. V. Schaffer, ‘Stochastic Gene Expression in a Lentiviral Positive-Feedback Loop: HIV-1 Tat Fluctuations Drive Phenotypic Diversity’, Cell, vol. 122, no. 2, pp. 169–182, Jul. 2005, doi: 10.1016/j.cell.2005.06.006.
3. N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, ‘Bacterial Persistence as a Phenotypic Switch’, Science, vol. 305, no. 5690, pp. 1622–1625, Sep. 2004, doi: 10.1126/science.1099390.
4. O. Symmons and A. Raj, ‘What’s Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism’, Molecular Cell, vol. 62, no. 5, pp. 788–802, Jun. 2016, doi: 10.1016/j.molcel.2016.05.023.
5. I. Tirosh, ‘Stochastic transitions as a major source of cancer heterogeneity’, Nat Rev Genet, vol. 23, no. 10, pp. 582–583, Oct. 2022, doi: 10.1038/s41576-022-00508-2.
6. A. A. Cohen et al., ‘Dynamic Proteomics of Individual Cancer Cells in Response to a Drug’, Science, vol. 322, no. 5907, pp. 1511–1516, Dec. 2008, doi: 10.1126/science.1160165.
7. A. Brock, H. Chang, and S. Huang, ‘Non-genetic heterogeneity — a mutation-independent driving force for the somatic evolution of tumours’, Nat Rev Genet, vol. 10, no. 5, pp. 336–342, May 2009, doi: 10.1038/nrg2556.
8. P. B. Gupta et al., ‘Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells’, Cell, vol. 146, no. 4, pp. 633–644, Aug. 2011, doi: 10.1016/j.cell.2011.07.026.
9. R. Bahar et al., ‘Increased cell-to-cell variation in gene expression in ageing mouse heart’, Nature, vol. 441, no. 7096, pp. 1011–1014, Jun. 2006, doi: 10.1038/nature04844.
10. W. Zakrzewski, M. Dobrzyński, M. Szymonowicz, and Z. Rybak, ‘Stem cells: past, present, and future’, Stem Cell Res Ther, vol. 10, no. 1, p. 68, Dec. 2019, doi: 10.1186/s13287-019-1165-5.
11. A. M. Klein et al., ‘Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells’, Cell, vol. 161, no. 5, pp. 1187–1201, May 2015, doi: 10.1016/j.cell.2015.04.044.
12. F. Paul et al., ‘Transcriptional Heterogeneity and Lineage Commitment in Myeloid Progenitors’, Cell, vol. 163, no. 7, pp. 1663–1677, Dec. 2015, doi: 10.1016/j.cell.2015.11.013.
13. N. Swain, M. Thakur, J. Pathak, and B. Swain, ‘SOX2, OCT4 and NANOG: The core embryonic stem cell pluripotency regulators in oral carcinogenesis’, J Oral Maxillofac Pathol, vol. 24, no. 2, p. 368, 2020, doi: 10.4103/jomfp.JOMFP_22_20.
14. H. Niwa, K. Ogawa, D. Shimosato, and K. Adachi, ‘A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells’, Nature, vol. 460, no. 7251, pp. 118–122, Jul. 2009, doi: 10.1038/nature08113.
15. K. Mitsui et al., ‘The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells’, Cell, vol. 113, no. 5, pp. 631–642, May 2003, doi: 10.1016/S0092-8674(03)00393-3.
16. I. Chambers et al., ‘Nanog safeguards pluripotency and mediates germline development’, Nature, vol. 450, no. 7173, pp. 1230–1234, Dec. 2007, doi: 10.1038/nature06403.
17. E. Abranches et al., ‘Stochastic NANOG fluctuations allow mouse embryonic stem cells to explore pluripotency’, Development, vol. 141, no. 14, pp. 2770–2779, Jul. 2014, doi: 10.1242/dev.108910.
18. H. Ochiai et al., ‘Genome-wide kinetic properties of transcriptional bursting in mouse embryonic stem cells’, Sci. Adv., vol. 6, no. 25, p. eaaz6699, Jun. 2020, doi: 10.1126/sciadv.aaz6699.
19. H. Ochiai, T. Sugawara, T. Sakuma, and T. Yamamoto, ‘Stochastic promoter activation affects Nanog expression variability in mouse embryonic stem cells’, Sci Rep, vol. 4, no. 1, p. 7125, Nov. 2014, doi: 10.1038/srep07125.
20. E. Tunnacliffe and J. R. Chubb, ‘What Is a Transcriptional Burst?’, Trends in Genetics, vol. 36, no. 4, pp. 288–297, Apr. 2020, doi: 10.1016/j.tig.2020.01.003.
21. A. M. Corrigan, E. Tunnacliffe, D. Cannon, and J. R. Chubb, ‘A continuum model of transcriptional bursting’, eLife, vol. 5, p. e13051, Feb. 2016, doi: 10.7554/eLife.13051.
22. Y. Wang, T. Ni, W. Wang, and F. Liu, ‘Gene transcription in bursting: a unified mode for realizing accuracy and stochasticity: Gene transcription in bursting’, Biol Rev, vol. 94, no. 1, pp. 248–258, Feb. 2019, doi: 10.1111/brv.12452.
23. T. Kalmar et al., ‘Regulated Fluctuations in Nanog Expression Mediate Cell Fate Decisions in Embryonic Stem Cells’, PLoS Biol, vol. 7, no. 7, p. e1000149, Jul. 2009, doi: 10.1371/journal.pbio.1000149.
24. K. A. U. Gonzales et al., ‘Deterministic Restriction on Pluripotent State Dissolution by Cell-Cycle Pathways’, Cell, vol. 162, no. 3, pp. 564–579, Jul. 2015, doi: 10.1016/j.cell.2015.07.001.
25. J. Jang et al., ‘Control over single-cell distribution of G1 lengths by WNT governs pluripotency’, PLoS Biol, vol. 17, no. 9, p. e3000453, Sep. 2019, doi: 10.1371/journal.pbio.3000453.
26. D. Coronado et al., ‘A short G1 phase is an intrinsic determinant of naïve embryonic stem cell pluripotency’, Stem Cell Research, vol. 10, no. 1, pp. 118–131, Jan. 2013, doi: 10.1016/j.scr.2012.10.004.
27. S. Pennings, K. J. Liu, and H. Qian, ‘The Stem Cell Niche: Interactions between Stem Cells and Their Environment’, Stem Cells International, vol. 2018, pp. 1–3, Oct. 2018, doi: 10.1155/2018/4879379.
28. N. B. Leimkühler and R. K. Schneider, ‘Inflammatory bone marrow microenvironment’, Hematology, vol. 2019, no. 1, pp. 294–302, Dec. 2019, doi: 10.1182/hematology.2019000045.
29. G. S. Ali, S. G. Palusa, M. Golovkin, J. Prasad, J. L. Manley, and A. S. N. Reddy, ‘Regulation of Plant Developmental Processes by a Novel Splicing Factor’, PLoS ONE, vol. 2, no. 5, p. e471, May 2007, doi: 10.1371/journal.pone.0000471.
30. K. R. Mesa et al., ‘Homeostatic Epidermal Stem Cell Self-Renewal Is Driven by Local Differentiation’, Cell Stem Cell, vol. 23, no. 5, pp. 677-686.e4, Nov. 2018, doi: 10.1016/j.stem.2018.09.005.
31. Q. Smith, E. Stukalin, S. Kusuma, S. Gerecht, and S. X. Sun, ‘Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics’, Sci Rep, vol. 5, no. 1, p. 12617, Jul. 2015, doi: 10.1038/srep12617.
32. F. M. Watt and A. B. L. M. Hogan, ‘Out of Eden: Stem Cells and Their Niches’, Science, vol. 287, no. 5457, pp. 1427–1430, Feb. 2000, doi: 10.1126/science.287.5457.1427.
33. F. Chowdhury et al., ‘Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells’, Nature Mater, vol. 9, no. 1, pp. 82–88, Jan. 2010, doi: 10.1038/nmat2563.
34. D. Li et al., ‘Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions’, Journal of Cell Biology, vol. 191, no. 3, pp. 631–644, Nov. 2010, doi: 10.1083/jcb.201006094.
35. Y.-C. Toh, J. Xing, and H. Yu, ‘Modulation of integrin and E-cadherin-mediated adhesions to spatially control heterogeneity in human pluripotent stem cell differentiation’, Biomaterials, vol. 50, pp. 87–97, May 2015, doi: 10.1016/j.biomaterials.2015.01.019.
36. I. G. Johnston, B. Gaal, R. P. D. Neves, T. Enver, F. J. Iborra, and N. S. Jones, ‘Mitochondrial Variability as a Source of Extrinsic Cellular Noise’, PLoS Comput Biol, vol. 8, no. 3, p. e1002416, Mar. 2012, doi: 10.1371/journal.pcbi.1002416.
37. S.-M. Ho, A. Johnson, P. Tarapore, V. Janakiram, X. Zhang, and Y.-K. Leung, ‘Environmental Epigenetics and Its Implication on Disease Risk and Health Outcomes’, ILAR Journal, vol. 53, no. 3–4, pp. 289–305, Dec. 2012, doi: 10.1093/ilar.53.3-4.289.
38. P. Dong and Z. Liu, ‘Shaping development by stochasticity and dynamics in gene regulation’, Open Biol., vol. 7, no. 5, p. 170030, May 2017, doi: 10.1098/rsob.170030.
39. S. Ito, A. C. D’Alessio, O. V. Taranova, K. Hong, L. C. Sowers, and Y. Zhang, ‘Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification’, Nature, vol. 466, no. 7310, pp. 1129–1133, Aug. 2010, doi: 10.1038/nature09303.
40. A. Gola and E. Fuchs, ‘Environmental control of lineage plasticity and stem cell memory’, Current Opinion in Cell Biology, vol. 69, pp. 88–95, Apr. 2021, doi: 10.1016/j.ceb.2020.12.015.
41. N. Eling, M. D. Morgan, and J. C. Marioni, ‘Challenges in measuring and understanding biological noise’, Nat Rev Genet, vol. 20, no. 9, pp. 536–548, Sep. 2019, doi: 10.1038/s41576-019-0130-6.
Data Availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
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- Volume Title
- Proceedings of the 2nd International Conference on Modern Medicine and Global Health
- ISBN (Print)
- 978-1-83558-395-1
- ISBN (Online)
- 978-1-83558-396-8
- Published Date
- 26 April 2024
- Series
- Theoretical and Natural Science
- ISSN (Print)
- 2753-8818
- ISSN (Online)
- 2753-8826
- DOI
- 10.54254/2753-8818/35/20240930
- Copyright
- 26 April 2024
- Open Access
- This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited