Single-cell multi-omics defines the cell-type-specific impact of splicing aberrations in human hematopoietic clonal outgrowths.
BAX
RNA-seq
SF3B1
clonal hematopoiesis
genotyping
long-read sequencing
multi-omics
myelodysplastic syndrome
single cell
splicing
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
07 09 2023
07 09 2023
Historique:
received:
18
10
2022
revised:
28
05
2023
accepted:
18
07
2023
pmc-release:
07
09
2024
medline:
11
9
2023
pubmed:
16
8
2023
entrez:
15
8
2023
Statut:
ppublish
Résumé
RNA splicing factors are recurrently mutated in clonal blood disorders, but the impact of dysregulated splicing in hematopoiesis remains unclear. To overcome technical limitations, we integrated genotyping of transcriptomes (GoT) with long-read single-cell transcriptomics and proteogenomics for single-cell profiling of transcriptomes, surface proteins, somatic mutations, and RNA splicing (GoT-Splice). We applied GoT-Splice to hematopoietic progenitors from myelodysplastic syndrome (MDS) patients with mutations in the core splicing factor SF3B1. SF3B1
Identifiants
pubmed: 37582363
pii: S1934-5909(23)00257-6
doi: 10.1016/j.stem.2023.07.012
pmc: PMC10528176
mid: NIHMS1921094
pii:
doi:
Substances chimiques
RNA Splice Sites
0
RNA Splicing Factors
0
Phosphoproteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1262-1281.e8Subventions
Organisme : NCI NIH HHS
ID : R33 CA267219
Pays : United States
Organisme : NINDS NIH HHS
ID : UG3 NS132139
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG011014
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128239
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL157387
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA251138
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA242020
Pays : United States
Organisme : NHLBI NIH HHS
ID : F30 HL156496
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007739
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests F.G. serves as a consultant for S2 Genomics Inc. X.D., J.B., A.W.D., S.H., S.J., and E.H. are employees of Oxford Nanopore Technologies Inc. and are shareholders and/or share option holders. I.M.G. serves on the advisory or consulting board of Bristol Myers Squibb, Takeda, Janssen, Sanofi, Novartis, Amgen, Celgene, Cellectar, Pfizer, Menarini Silicon Biosystems, Oncopeptides, The Binding Site, GlazoSmithKlein, AbbVie, Adaptive, and 10x Genomics. O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc., Merck, Pfizer, and Janssen, and O.A.-W. is on the Scientific Advisory Board of Envisagenics Inc. and AIChemy. O.A.-W. has received prior research funding from H3B Biomedicine and LOXO Oncology unrelated to the current manuscript. D.A.L. has served as a consultant for AbbVie, AstraZeneca, and Illumina and is on the Scientific Advisory Board of Mission Bio, Pangea, Alethiomics, and C2i Genomics; D.A.L. has received prior research funding from BMS, 10x Genomics, Ultima Genomics, and Illumina unrelated to the current manuscript.
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