Biology subjects

Langhinrichs, M.

Publications and source records attributed to Langhinrichs, M..

3 recordsLinked to original sources

bioRxiv2025

Clonal Dynamics in the Male Germline from Development to Next Generation

Germ cells secure the continuity and evolutionary potential of species. Yet how reproductive success is allocated among the founder cells of the mammalian male germline, the primordial germ cells (PGCs), remains unknown. Here, we quantitatively traced individual PGCs, non-invasively barcoded in mouse embryos, across their establishment, lifelong maintenance within the testis, spermatogenesis, and transmission to the next generation. We found that highly skewed clonal contributions arise from a very early stochastic bottleneck during migration to the developing testes and remain stable throughout adult reproductive life. Reproductive success during adulthood was proportional to the embryonically established PGC clone size. Mathematical modeling shows that the patchy compartmentalization of PGC clones within the extended thin seminiferous tubules maintain clonal diversity and safeguard against the expansion of clones that gain a selective advantage. These findings uncover fundamental principles governing the development, stability, and evolutionary transmission of the mammalian germline.

developmental biology↗

bioRxiv2024

Holistic genetic barcoding reveals a lineage tree of tissue macrophage development

Tissue macrophages are crucial for organ development and homeostasis, yet the developmental routes leading to tissue macrophages remain controversial. By combining unbiased Polylox barcoding with computational inference, we comprehensively mapped tissue macrophage ontogeny in mice from gastrulation to adult organs. Our data reveal a lineage tree of all tissue macrophages. This tree originates from a pan-hematopoietic progenitor at embryonic day (E)6.5 and branches, via oligolineage progenitors (E7.5-E9.5), into organ-specific macrophage lineages by E10.5. Barcode analysis in embryonic tissues and adult organ fragments suggests that local macrophage colonies, formed by organ-specific progenitors, persist into adulthood. Indeed, spatial fate mapping with Polytope barcoding detects local Kupffer cell colonies of the size predicted by the lineage tree model. Our findings uncover the origin of tissue-resident macrophages from a lineage tree, and show how holistic barcoding can comprehensively map complex cellular lineage specification. One-Sentence SummaryHolistic, time- and space-resolved barcoding in the embryo reveals a unified lineage tree for all tissue macrophages, generating local macrophage colonies persisting in adult organs.

developmental biology↗

bioRxiv2020

Size-independent mRNA synthesis and chromatin-based partitioning mechanisms generate and maintain constant amounts of protein per cell

Biosynthesis scales with cell size such that protein concentrations generally remain constant as cells grow. As an exception, synthesis of the cell-cycle inhibitor Whi5 sub-scales with cell size so that its concentration is lower in larger cells to promote cell-cycle entry. Here, we find that a transcriptional control uncouples Whi5 synthesis from cell size and, screening for similar genes, identify histones as the major class of sub-scaling transcripts besides WHI5. Histone synthesis is thereby matched to genome content rather than cell size. Such sub-scaling proteins are challenged by asymmetric cell division because proteins are typically partitioned in proportion to new-born cell volume. To avoid this fate, Whi5 uses chromatin-binding to partition similar protein amounts to each new-born cell regardless of cell size. Finally, disrupting both Whi5 synthesis and chromatin-based partitioning compromises G1 size control. Thus, specific transcriptional and partitioning mechanisms determine protein sub-scaling to control cell size.

cell biology↗