He, X. C. | Search bioRxiv

bioRxiv2024

Characterization of Multicellular Niches Supporting Hematopoietic Stem Cells Within Distinct Zones

Previous studies of hematopoietic stem cells (HSCs) primarily focused on single cell-based niche models, yielding fruitful but conflicting findings1-5. Here we report our investigation on the fetal liver (FL) as the primary fetal hematopoietic site using spatial transcriptomics. Our study reveals two distinct niches: the portal-vessel (PV) niche and the sinusoidal niche. The PV niche, composing N-cadherin (N-cad)HiPdgfr+ mesenchymal stromal cells (MSCs), endothelial cells (ECs), and N-cadLoAlbumin+ hepatoblasts, maintains quiescent and multipotential FL-HSCs. Conversely, the sinusoidal niche, comprising ECs, hepatoblasts and hepatocytes, as well as potential macrophages and megakaryocytes, supports proliferative FL-HSCs biased towards myeloid lineages. Unlike prior reports on the role of Cxcl12, with its depletion from vessel-associated stromal cells leading to 80% of HSCs reduction in the adult bone marrow (BM)6,7, depletion of Cxcl12 via Cdh2CreERT (encoding N-cad) induces altered localization of HSCs from the PV to the sinusoidal niches, resulting in an increase of HSC number but with myeloid-bias. Similarly, we discovered that adult BM encompasses two niches within different zones, each composed of multi-cellular components: trabecular bone area (TBA, or metaphysis) supporting deep-quiescent HSCs, and central marrow (CM, or diaphysis) fostering heterogenous proliferative HSCs. This study transforms our understanding of niches by shifting from single cell-based to multicellular components within distinct zones, illuminating the intricate regulation of HSCs tailored to their different cycling states.

developmental biology↗

bioRxiv2019

A Holistic Analysis of the Intestinal Stem Cell Niche Network

Although many studies into the intestinal stem cell (ISC) niche have been carried out, they have focused on the role of a single cell type or molecular signal. However, no holistic comparisons of the predominant cell types and signals present within the intestinal mucosa have been conducted to date. We utilize bulk RNA sequencing to profile 20 different mucosal cell types covering four major cell categories: epithelial, stromal, endothelial and immune. We further examined the stromal signaling environment using scRNAseq to provide a more comprehensive view of the signaling microenvironment within the intestinal mucosa. We identified the primary signals for the major ISC regulatory pathways and their respective cellular sources. Our analysis suggests that a niche network exists, with no single cell type being responsible for ISC self-renewal, proliferation, or differentiation; rather, each cell type within the network carries out specific functions in a highly cooperative and coordinated manner.

cell biology↗