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Article

Ultra-Structural Imaging Provides 3D Organization of 46 Chromosomes of a Human Lymphocyte Prophase Nucleus

by
Atiqa Sajid
1,
El-Nasir Lalani
1,
Bo Chen
2,3,4,
Teruo Hashimoto
5,
Darren K. Griffin
6,
Archana Bhartiya
2,
George Thompson
5,†,
Ian K. Robinson
2,7 and
Mohammed Yusuf
1,2,*
1
Centre for Regenerative Medicine and Stem Cell Research, Aga Khan University, Karachi 74800, Pakistan
2
London Centre for Nanotechnology, University College London, London WC1H 0AH, UK
3
School of Materials Science and Engineering, Tongji University, Shanghai 201804, China
4
Key Laboratory of Performance Evolution and Control for Engineering Structures of the Ministry of Education, Tongji University, Shanghai 200092, China
5
Department of Materials, University of Manchester, Oxford Road, Manchester M13 9PL, UK
6
School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
7
Brookhaven National Laboratory, Upton, NY 11973, USA
*
Author to whom correspondence should be addressed.
†
Deceased.
Int. J. Mol. Sci. 2021, 22(11), 5987; https://doi.org/10.3390/ijms22115987
Submission received: 4 May 2021 / Revised: 21 May 2021 / Accepted: 23 May 2021 / Published: 1 June 2021
(This article belongs to the Special Issue Cytomolecular Organisation of the Nuclear Genome)
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Abstract

Three dimensional (3D) ultra-structural imaging is an important tool for unraveling the organizational structure of individual chromosomes at various stages of the cell cycle. Performing hitherto uninvestigated ultra-structural analysis of the human genome at prophase, we used serial block-face scanning electron microscopy (SBFSEM) to understand chromosomal architectural organization within 3D nuclear space. Acquired images allowed us to segment, reconstruct, and extract quantitative 3D structural information about the prophase nucleus and the preserved, intact individual chromosomes within it. Our data demonstrate that each chromosome can be identified with its homolog and classified into respective cytogenetic groups. Thereby, we present the first 3D karyotype built from the compact axial structure seen on the core of all prophase chromosomes. The chromosomes display parallel-aligned sister chromatids with familiar chromosome morphologies with no crossovers. Furthermore, the spatial positions of all 46 chromosomes revealed a pattern showing a gene density-based correlation and a neighborhood map of individual chromosomes based on their relative spatial positioning. A comprehensive picture of 3D chromosomal organization at the nanometer level in a single human lymphocyte cell is presented.
Keywords: cytogenetics; chromosome; chromosome territory; microscopy; three dimensions; serial block-face electron microscopy; prophase cytogenetics; chromosome; chromosome territory; microscopy; three dimensions; serial block-face electron microscopy; prophase
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MDPI and ACS Style

Sajid, A.; Lalani, E.-N.; Chen, B.; Hashimoto, T.; Griffin, D.K.; Bhartiya, A.; Thompson, G.; Robinson, I.K.; Yusuf, M. Ultra-Structural Imaging Provides 3D Organization of 46 Chromosomes of a Human Lymphocyte Prophase Nucleus. Int. J. Mol. Sci. 2021, 22, 5987. https://doi.org/10.3390/ijms22115987

AMA Style

Sajid A, Lalani E-N, Chen B, Hashimoto T, Griffin DK, Bhartiya A, Thompson G, Robinson IK, Yusuf M. Ultra-Structural Imaging Provides 3D Organization of 46 Chromosomes of a Human Lymphocyte Prophase Nucleus. International Journal of Molecular Sciences. 2021; 22(11):5987. https://doi.org/10.3390/ijms22115987

Chicago/Turabian Style

Sajid, Atiqa, El-Nasir Lalani, Bo Chen, Teruo Hashimoto, Darren K. Griffin, Archana Bhartiya, George Thompson, Ian K. Robinson, and Mohammed Yusuf. 2021. "Ultra-Structural Imaging Provides 3D Organization of 46 Chromosomes of a Human Lymphocyte Prophase Nucleus" International Journal of Molecular Sciences 22, no. 11: 5987. https://doi.org/10.3390/ijms22115987

APA Style

Sajid, A., Lalani, E.-N., Chen, B., Hashimoto, T., Griffin, D. K., Bhartiya, A., Thompson, G., Robinson, I. K., & Yusuf, M. (2021). Ultra-Structural Imaging Provides 3D Organization of 46 Chromosomes of a Human Lymphocyte Prophase Nucleus. International Journal of Molecular Sciences, 22(11), 5987. https://doi.org/10.3390/ijms22115987

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