AI Article Synopsis

  • Scientists are trying to understand how certain immune cells, called lymphocytes, develop in our bodies.
  • They found that there are different paths these cells can take, and new types of cells called multi-lymphoid progenitors (MLPs) form before becoming either NK, ILC, T cells, or B cells.
  • The way these cells grow and develop is really different depending on the kind of immune cell they will become, and the scientists discovered new important steps and controls in this process.

Article Abstract

The developmental cartography of human lymphopoiesis remains incompletely understood. Here, we establish a multimodal map demonstrating that lymphoid specification follows independent direct or stepwise hierarchic routes converging toward the emergence of newly characterized CD117 multi-lymphoid progenitors (MLPs) that undergo a proliferation arrest before entering the CD127 (NK/ILC/T) or CD127 (B) lymphoid pathways. While the differentiation of CD127 early lymphoid progenitors is mainly driven by Flt3 signaling, emergence of their CD127 counterparts is regulated cell-intrinsically and depends exclusively on the divisional history of their upstream precursors, including hematopoietic stem cells. Further, transcriptional mapping of differentiation trajectories reveals that whereas myeloid granulomonocytic lineages follow continuous differentiation pathways, lymphoid trajectories are intrinsically discontinuous and characterized by sequential waves of cell proliferation allowing pre-commitment amplification of lymphoid progenitor pools. Besides identifying new lymphoid specification pathways and regulatory checkpoints, our results demonstrate that NK/ILC/T and B lineages are under fundamentally distinct modes of regulation. (149 words).

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520540PMC
http://dx.doi.org/10.1016/j.isci.2023.107890DOI Listing

Publication Analysis

Top Keywords

cartography human
8
human lymphopoiesis
8
lymphoid specification
8
lymphoid
5
multimodal cartography
4
lymphopoiesis reveals
4
reveals t/nk/ilc
4
t/nk/ilc lineages
4
lineages subjected
4
subjected differential
4

Similar Publications

Long-term risks of gene therapy are not fully understood. In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy trials. The trials employed integrating gammaretroviral or lentiviral vectors to deliver engineered receptors to target HIV-1 infection or cancer.

View Article and Find Full Text PDF

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.

View Article and Find Full Text PDF

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

View Article and Find Full Text PDF

The ongoing emergence of SARS-CoV-2 variants, combined with antigen exposures from different waves and vaccinations, poses challenges in updating COVID-19 vaccine antigens. We collected 206 sera from individuals with vaccination-only, hybrid immunity, and single or repeated omicron post-vaccination infections (PVIs), including non-JN.1 and JN.

View Article and Find Full Text PDF

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing identifies rare populations that express specific marker transcript combinations, traditional flow sorting requires cell surface markers with high-fidelity antibodies, limiting our ability to interrogate these populations. In addition, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!