Dataset Information

Single-Cell Analysis of Neonatal HSC Ontogeny Reveals Gradual and Uncoordinated Transcriptional Reprogramming that Begins before Birth.

ABSTRACT: Fetal and adult hematopoietic stem cells (HSCs) have distinct proliferation rates, lineage biases, gene expression profiles, and gene dependencies. Although these differences are widely recognized, it is not clear how the transition from fetal to adult identity is coordinated. Here we show that murine HSCs and committed hematopoietic progenitor cells (HPCs) undergo a gradual, rather than precipitous, transition from fetal to adult transcriptional states. The transition begins prior to birth and is punctuated by a late prenatal spike in type I interferon signaling that promotes perinatal HPC expansion and sensitizes progenitors to the leukemogenic FLT3^ITD mutation. Most other changes in gene expression and enhancer activation are imprecisely timed and poorly coordinated. Thus, heterochronic enhancer elements, and their associated transcripts, are activated independently of one another rather than as part of a robust network. This simplifies the regulatory programs that guide neonatal HSC/HPC ontogeny, but it creates heterogeneity within these populations.

SUBMITTER: Li Y

PROVIDER: S-EPMC7655695 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Single-Cell Analysis of Neonatal HSC Ontogeny Reveals Gradual and Uncoordinated Transcriptional Reprogramming that Begins before Birth.

Li Yanan Y Kong Wenjun W Yang Wei W Patel Riddhi M RM Casey Emily B EB Okeyo-Owuor Theresa T White J Michael JM Porter Shaina N SN Morris Samantha A SA Magee Jeffrey A JA

Cell stem cell 20200820 5

Fetal and adult hematopoietic stem cells (HSCs) have distinct proliferation rates, lineage biases, gene expression profiles, and gene dependencies. Although these differences are widely recognized, it is not clear how the transition from fetal to adult identity is coordinated. Here we show that murine HSCs and committed hematopoietic progenitor cells (HPCs) undergo a gradual, rather than precipitous, transition from fetal to adult transcriptional states. The transition begins prior to birth and ...[more]

PMID: 32822583

Similar Datasets

Project description:Development of prefrontal and other higher-order association cortices is associated with widespread changes in the cortical transcriptome, particularly during the transitions from prenatal to postnatal development, and from early infancy to later stages of childhood and early adulthood. However, the timing and longitudinal trajectories of neuronal gene expression programs during these periods remain unclear in part because of confounding effects of concomitantly occurring shifts in neuron-to-glia ratios. Here, we used cell type-specific chromatin sorting techniques for genome-wide profiling of a histone mark associated with transcriptional regulation--H3 with trimethylated lysine 4 (H3K4me3)--in neuronal chromatin from 31 subjects from the late gestational period to 80 years of age. H3K4me3 landscapes of prefrontal neurons were developmentally regulated at 1,157 loci, including 768 loci that were proximal to transcription start sites. Multiple algorithms consistently revealed that the overwhelming majority and perhaps all of developmentally regulated H3K4me3 peaks were on a unidirectional trajectory defined by either rapid gain or loss of histone methylation during the late prenatal period and the first year after birth, followed by similar changes but with progressively slower kinetics during early and later childhood and only minimal changes later in life. Developmentally downregulated H3K4me3 peaks in prefrontal neurons were enriched for Paired box (Pax) and multiple Signal Transducer and Activator of Transcription (STAT) motifs, which are known to promote glial differentiation. In contrast, H3K4me3 peaks subject to a progressive increase in maturing prefrontal neurons were enriched for activating protein-1 (AP-1) recognition elements that are commonly associated with activity-dependent regulation of neuronal gene expression. We uncovered a developmental program governing the remodeling of neuronal histone methylation landscapes in the prefrontal cortex from the late prenatal period to early adolescence, which is linked to cis-regulatory sequences around transcription start sites.

Dataset Information

Single-Cell Analysis of Neonatal HSC Ontogeny Reveals Gradual and Uncoordinated Transcriptional Reprogramming that Begins before Birth.

Publications

Single-Cell Analysis of Neonatal HSC Ontogeny Reveals Gradual and Uncoordinated Transcriptional Reprogramming that Begins before Birth.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets