Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

Опубликована: Фев. 3, 2025

Current in vitro models of developmental blood formation lack spatio-temporal accuracy and weakly replicate successive waves hematopoiesis. Herein, we describe a mouse embryonic stem cell (SC)-derived 3D hemogenic gastruloid (hGx) that captures multi-wave formation, progenitor specification from endothelium (HE), generates hematopoietic SC precursors capable short-term engraftment immunodeficient mice upon maturation an adrenal niche. We took advantage the hGx model to interrogate origins infant acute myeloid leukemia (infAML). focused on MNX1-driven leukemia, representing commonest genetic abnormality unique group. Enforced MNX1 expression promotes expansion transformation yolk sac-like erythroid-myeloid progenitors (EMP) at HE-to-hematopoietic transition faithfully recapitulate patient transcriptional signatures. By combining phenotypic, functional profiling, including single-cell level, establish as useful new for study normal leukemic hematopoiesis .

Язык: Английский

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

Опубликована: Фев. 3, 2025

Current in vitro models of developmental blood formation lack spatio-temporal accuracy and weakly replicate successive waves hematopoiesis. Herein, we describe a mouse embryonic stem cell (SC)-derived 3D hemogenic gastruloid (hGx) that captures multi-wave formation, progenitor specification from endothelium (HE), generates hematopoietic SC precursors capable short-term engraftment immunodeficient mice upon maturation an adrenal niche. We took advantage the hGx model to interrogate origins infant acute myeloid leukemia (infAML). focused on MNX1-driven leukemia, representing commonest genetic abnormality unique group. Enforced MNX1 expression promotes expansion transformation yolk sac-like erythroid-myeloid progenitors (EMP) at HE-to-hematopoietic transition faithfully recapitulate patient transcriptional signatures. By combining phenotypic, functional profiling, including single-cell level, establish as useful new for study normal leukemic hematopoiesis .

Язык: Английский

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Окт. 7, 2022

ABSTRACT Current in vitro models of developmental blood formation lack spatio-temporal accuracy and weakly replicate successive waves hematopoiesis. Herein, we describe a mouse embryonic stem cell (SC)-derived 3D hemogenic gastruloid (haemGx) that captures multi-wave formation, progenitor specification from endothelium (HE), generates hematopoietic progenitors capable short-term engraftment immunodeficient mice upon maturation an vivo niche. We took advantage the haemGx model to interrogate origins infant acute myeloid leukemia (infAML). focused on MNX1-driven leukemia, representing commonest genetic abnormality unique group. Enforced MNX1 expression promotes expansion transformation yolk sac-like erythroid-myeloid at HE-to-hematopoietic transition faithfully recapitulate patient transcriptional signatures. By combining phenotypic, functional profiling, including single-cell level, establish as useful new for study normal leukemic

Язык: Английский