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CTNNB1 encodes beta-catenin, which plays a crucial role in Wnt signaling pathway. Mutations in CTNNB1 involve in tumor developing, Primary Aldosteronism, Neurodevelopmental disorders (NDDs), etc. NDDs is a class of disorders that impact brain development and function, manifesting symptom including autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia (SCZ), and epilepsy. Here, we generated an iPSC line (CTUi005-A) from a patient diagnosed with NDDs, carrying a heterozygous mutation of the CTNNB1 gene. CTUi005-A exhibits typical iPSC characteristics, and holds potential as a cellular tool for investigating the pathogenic mechanisms underlying NDDs.

Abstract Human hematopoiesis starts at early yolk sac and undergoes site- and stage-specific changes over development. The intrinsic mechanism underlying property changes in hematopoiesis ontogeny remains poorly understood. Here, we analyzed single-cell transcriptome of human primary hematopoietic stem/progenitor cells (HSPCs) at different developmental stages, including yolk-sac (YS), AGM, fetal liver (FL), umbilical cord blood (UCB) and adult peripheral blood (PB) mobilized HSPCs. These stage-specific HSPCs display differential intrinsic properties, such as metabolism, self-renewal, differentiating potentialities etc. We then generated highly co-related gene regulatory network (GRNs) modules underlying the differential HSC key properties. Particularly, we identified GRNs and key regulators controlling lymphoid potentiality, self-renewal as well as aerobic respiration in human HSCs. Introducing selected regulators promotes key HSC functions in HSPCs derived from human pluripotent stem cells. Therefore, GRNs underlying key intrinsic properties of human HSCs provide a valuable guide to generate fully functional HSCs in vitro.