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[Preprint]. 2025 Jan 27:2025.01.24.25320911.
doi: 10.1101/2025.01.24.25320911.

Somatic and Stem Cell Bank to Study the Contribution of African Ancestry to Dementia: African iPSC Initiative

Mahmoud B Maina  1   2 , Murtala B Isah  1   3 , Jacob A Marsh  4 , Zaid Muhammad  1   2 , Larema Babazau  1 , Abdulrahman Alkhamis Idris  1 , Ekaterina Aladyeva  5 , Nadia Miller  4 , Emma Starr  4 , Katherine J Miller  4 , Scott Lee  4 , Miguel Minaya  4 , Selina Wray  6 , Oscar Harari  5 , Baba W Goni  1 , Louise C Serpell  2 , Celeste M Karch  4
Affiliations

Somatic and Stem Cell Bank to Study the Contribution of African Ancestry to Dementia: African iPSC Initiative

Mahmoud B Maina et al. medRxiv. .

Update in

Abstract

Introduction: Africa, home to 1.4 billion people and the highest genetic diversity globally, harbors unique genetic variants crucial for understanding complex diseases like neurodegenerative disorders. However, African populations remain underrepresented in induced pluripotent stem cell (iPSC) collections, limiting the exploration of population-specific disease mechanisms and therapeutic discoveries.

Methods: To address this gap, we established an open-access African Somatic and Stem Cell Bank.

Results: In this initial phase, we generated 10 rigorously characterized iPSC lines from fibroblasts representing five Nigerian ethnic groups and both sexes. These lines underwent extensive profiling for pluripotency, genetic stability, differentiation potential, and Alzheimer's disease and Parkinson's disease risk variants. CRISPR/Cas9 technology was used to introduce frontotemporal dementia-associated MAPT mutations (P301L and R406W).

Discussion: This collection offers a renewable, genetically diverse resource to investigate disease pathogenicity in African populations, facilitating breakthroughs in neurodegenerative research, drug discovery, and regenerative medicine.

Keywords: African ancestry; Alzheimer’s disease; CRISPR/Cas9; Induced pluripotent stem cells; Parkinson’s disease; cell bank; fibroblasts; frontotemporal dementia; polygenic risk scores.

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Conflict of interest statement

Conflict of Interest Statement The authors have no conflicts of interest to declare.

Figures

Figure 1:
Figure 1:. Establishing an African Somatic and Stem Cell Bank.
A. Map of Nigeria Indicating biopsy collection site (yellow) in the state of Yobe. Ethnic groups participating in the study indicated along with their regional distribution. Pink square, Babur. Green hexagon, Fulfude. Red circle, Hausa. Blue star, Kanuri. Yellow triangle, Kare-Kare. B. Workflow to transform skin biopsies into fibroblasts and induced pluripotent stem cells (iPSC).
Figure 2:
Figure 2:. Characterization of iPSC lines from African Somatic and Stem Cell Bank.
Representative characterization data featuring iPSC BA-001.1 A. Phase-contrast images showing cultured iPSCs. B. qPCR for pluripotency markers. C. Immunocytochemistry for pluripotency markers OCT4, SOX2, SSEA4, and TRA-1–60. D. G-band karyotyping reveals no chromosomal abnormalities. See Supplemental Figures 1–10 for characterization of all iPSC described in this study.
Figure 3:
Figure 3:. Genomic Profiling of iPSC lines from African Somatic and Stem Cell Bank.
A. Workflow. B-I. Genetic analyses of iPSC. B. Principal component analysis (PCA) of common genetic variants measured in unique iPSC lines (gray, cohort) compared to 1000 Genomes reference: Africans (AFR), Admixed Americans (AMR), East Asians (EAS), Europeans (EUR), South Asians (SAS). C. Frequency of APOE genotypes among iPSC lines. D-I. Polygenic Risk Scores (PRS). D-E. Distribution of PRS represented using reference (salmon, REF) and iPSC samples (cyan, TRG). G-H. Distribution of PRS represented based on Nigerian ethnic group. D, G. PRS for Alzheimer’s disease (AD) including the APOE gene locus. E, H. PRS for AD excluding the APOE gene locus. F, I. PRS for Parkinson’s disease (PD). J. Principal component analysis of transcriptomic data generated from iPSCs (500 most variable gene transcripts). Blue, female. Red, male.
Figure 4:
Figure 4:. Genome engineering of the MAPT locus in iPSC BA-001.1.
A. Workflow. B-D. BA-001.1 was edited from MAPT WT/WT to MAPT P301L/WT using CRISPR/Cas9. Characterization for one of the resulting clones: BA-001.1.P301L Δ1D01. B. Sanger sequencing illustrating the heterozygous engineered SNP. C. Immunocytochemistry for pluripotency markers OCT4, SOX2, SSEA4, and TRA-1–60. D. G-band karyotyping reveals no chromosomal abnormalities. E-F. BA-001.1 was edited from MAPT WT/WT to MAPT R406W/WT using CRISPR/Cas9. Characterization for one of the resulting clones: BA-001.1.R406W Δ1C09. E. Sanger sequencing illustrating the heterozygous engineered SNP. F. Immunocytochemistry for pluripotency markers OCT4, SOX2, SSEA4, and TRA1. G. G-band karyotyping reveals no chromosomal abnormalities.
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