Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders

Nickesha C Anderson; Pin-Fang Chen; Kesavan Meganathan; Wardiya Afshar Saber; Andrew J Petersen; Anita Bhattacharyya; Kristen L Kroll; Mustafa Sahin; Cross-IDDRC Human Stem Cell Working Group

doi:10.1016/j.stemcr.2021.03.025

Balancing serendipity and reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders

Stem Cell Reports. 2021 Jun 8;16(6):1446-1457. doi: 10.1016/j.stemcr.2021.03.025. Epub 2021 Apr 15.

Authors

Nickesha C Anderson¹, Pin-Fang Chen¹, Kesavan Meganathan², Wardiya Afshar Saber¹, Andrew J Petersen³, Anita Bhattacharyya⁴, Kristen L Kroll⁵, Mustafa Sahin⁶; Cross-IDDRC Human Stem Cell Working Group

Affiliations

¹ Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
² Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
³ Waisman Center, University of Wisconsin, Madison, WI 53705, USA.
⁴ Waisman Center, University of Wisconsin, Madison, WI 53705, USA; Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA. Electronic address: bhattacharyy@waisman.wisc.edu.
⁵ Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: kkroll@wustl.edu.
⁶ Department of Neurology, Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: mustafa.sahin@childrens.harvard.edu.

Abstract

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs. Based upon these findings, we propose recommendations for best practices that can be adopted by research scientists as well as journal editors.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Cell Differentiation*
Cellular Reprogramming*
Genetic Variation*
Humans
Induced Pluripotent Stem Cells*
Intellectual Disability / etiology*
Models, Biological
Neurons
Reproducibility of Results

Abstract

Publication types

MeSH terms

Grants and funding