Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ)-Center for Molecular Biology of Heidelberg University (ZMBH) Alliance, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.
Blood. 2021 Jun 10;137(23):3218-3224. doi: 10.1182/blood.2020007876.
Hematopoietic stem cells (HSCs) and distinct multipotent progenitor (MPP) populations (MPP1-4) contained within the Lin-Sca-1+c-Kit+ (LSK) compartment have previously been identified using diverse surface-marker panels. Here, we phenotypically define and functionally characterize MPP5 (LSK CD34+CD135-CD48-CD150-). Upon transplantation, MPP5 supports initial emergency myelopoiesis followed by stable contribution to the lymphoid lineage. MPP5, capable of generating MPP1-4 but not HSCs, represents a dynamic and versatile component of the MPP network. To characterize all hematopoietic stem and progenitor cells, we performed RNA-sequencing (RNA-seq) analysis to identify specific transcriptomic landscapes of HSCs and MPP1-5. This was complemented by single-cell RNA-seq analysis of LSK cells to establish the differentiation trajectories from HSCs to MPP1-5. In agreement with functional reconstitution activity, MPP5 is located immediately downstream of HSCs but upstream of the more committed MPP2-4. This study provides a comprehensive analysis of the LSK compartment, focusing on the functional and molecular characteristics of the newly defined MPP5 subset.
造血干细胞（HSCs）和不同的多能祖细胞（MPP）群体（MPP1-4）包含在 Lin-Sca-1+c-Kit+（LSK）区室中，之前已经使用多种表面标志物组合进行了鉴定。在这里，我们通过表型定义和功能表征来鉴定 MPP5（LSK CD34+CD135-CD48-CD150-）。移植后，MPP5 支持初始紧急骨髓生成，随后稳定地贡献于淋巴谱系。MPP5 能够产生 MPP1-4，但不能产生 HSCs，它代表了 MPP 网络的一个动态和多功能组成部分。为了表征所有造血干细胞和祖细胞，我们进行了 RNA 测序（RNA-seq）分析，以鉴定 HSCs 和 MPP1-5 的特定转录组图谱。这通过 LSK 细胞的单细胞 RNA-seq 分析得到了补充，以建立从 HSCs 到 MPP1-5 的分化轨迹。与功能重建活性一致，MPP5 位于 HSCs 的下游，但位于更具定向性的 MPP2-4 的上游。这项研究提供了对 LSK 区室的全面分析，重点是新定义的 MPP5 亚群的功能和分子特征。
