PUBLICATION
Crip2 preserves hematopoietic stem and progenitor cell production through inhibition of Notch signals
- Authors
- Aleman, A.G., Ulloa, B., Nayak, R., Ford, C., Potts, K.S., de Sena-Tomás, C., Vicioso, C., Rangaswamy, U., Elias, H.K., Kharas, M.G., Sanges, R., Bowman, T., Targoff, K.L.
- ID
- ZDB-PUB-260129-45
- Date
- 2026
- Source
- Development (Cambridge, England) : (Journal)
- Registered Authors
- Bowman, Teresa, Targoff, Kimara
- Keywords
- Crip2, HSPC, Hemogenic endothelium, Notch, Zebrafish
- Datasets
- GEO:GSE300243
- MeSH Terms
- none
- PubMed
- 41601327 Full text @ Development
Citation
Aleman, A.G., Ulloa, B., Nayak, R., Ford, C., Potts, K.S., de Sena-Tomás, C., Vicioso, C., Rangaswamy, U., Elias, H.K., Kharas, M.G., Sanges, R., Bowman, T., Targoff, K.L. (2026) Crip2 preserves hematopoietic stem and progenitor cell production through inhibition of Notch signals. Development (Cambridge, England). :.
Abstract
Hematopoietic stem and progenitor cells (HSPCs) have multilineage potential and sustain long-term self-renewal. Deriving patient-specific HSPCs has immense therapeutic potential to overcome the shortage of compatible donors for transplantation. In zebrafish, hemogenic endothelium (HE) is a specialized collection of dorsal aortic endothelial cells (ECs) that give rise to HSPCs. Our data reveal cysteine rich intestinal protein 2 (crip2) has a previously unrecognized function in establishing the proper EC environment for HSPC specification. To investigate the requirement of crip2, we generated loss-of-function alleles in crip2 and crip3, a gene family member with cardiovascular expression. crip2-/-;crip3-/- (cripDM) embryos exhibit decreased HSPC emergence with impaired lineage derivative production. Single cell RNA-sequencing of kdrl:mCherry+ ECs reveals upregulation of vascular development signature and failure to repress Notch signals during the vital transition of HE specification to HSPC emergence. Moreover, our data underscore that inhibition of Notch promotes HSPC generation in cripDM embryos and Crip genes operate through NF-κB to limit Notch. Identification of Crip2 as a novel regulator of Notch repression in HE will enhance our understanding of cues necessary to improve human HSPC production in vitro.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping